Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MACROPHAGES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed1984

Macrophage subpopulations regulate intrathymic T-cell development. II: Ia-negative macrophages decrease thymocyte viability and proliferation by formation of thymocyte-macrophage-rosettes.

The influence of H2-Ia-negative macrophages (Ia-M phi) on thymocyte viability and proliferation was investigated. Peritoneal as well as Ia-M phi of thymic origin were used in this study and yielded similar results. Cocultivation of thymocyte with 4.5% Ia- M phi diminished thymocyte viability by about 70% and mitogen-induced proliferation by about 90% in comparison to control cultures without addition of M phi. These suppressive effects were related to rosette formation between thymocytes and Ia- M phi: more than 80% of Ia- M phi formed rosettes with immature thymocytes. Mature thymocytes (i.e. PNA-negative, steroid-resistant cells) rosetted in only 5% and were consequently not affected by M phi-mediated suppression. Since Cytochalasin B, known to inhibit rosette formation, abolished the suppressive effects of M phi, and supernatants of M phi cultures exhibited no inhibition of thymocytes, close cell contact (rosette) is apparently necessary for the inhibitory phenomenon. Suppression, however, seems to depend further on the functional state of the M phi: ingestion of carbon particles significantly diminished the inhibitory effect on thymocytes despite further presence of rosettes. The results suggest that Ia- M phi have a regulatory function within thymus physiology. While Ia+ M phi promote thymocyte proliferation as described elsewhere, the Ia- M phi may control the number and kind of thymocytes released by the thymus gland.

Animals↗
PubMed2003

Macrophage colony-stimulating factor in cooperation with transforming growth factor-beta1 induces the differentiation of CD34+ hematopoietic progenitor cells into Langerhans cells under serum-free conditions without granulocyte-macrophage colony-stimulating factor.

Macrophage colony-stimulating factor has not been considered as a factor responsible for dendritic cell or Langerhans cell development from hematopoietic progenitor cells. In this study, we examined whether macrophage colony-stimulating factor could be used instead of granulocyte-macrophage colony-stimulating factor for the in vitro development of Langerhans cells from hematopoietic progenitor cells. We replaced granulocyte-macrophage colony-stimulating factor with macrophage colony-stimulating factor from a serum-free culture containing granulocyte-macrophage colony-stimulating factor, stem cell factor, Flt3 ligand, tumor necrosis factor-alpha, and transforming growth factor-beta1. This serum-free culture medium containing macrophage colony-stimulating factor, but not granulocyte-macrophage colony-stimulating factor (macrophage colony-stimulating factor culture), could induce CD1a+ Birbeck granule+ Langerin+ E-cadherin+ factor-like XIIIa Langerhans cells. As a control, the culture of hematopoietic progenitor cells in this culture medium depleted of macrophage colony-stimulating factor or transforming growth factor-beta1 resulted in far fewer or null CD1a+ cells, respectively. Macrophage colony-stimulating factor increased the number of CD1a+ cells in a concentration-dependent fashion. These macrophage colony-stimulating factor-induced Langerhans cells were different from granulocyte-macrophage colony-stimulating factor-induced Langerhans cells in their decreased expression of CD11c and their immature phenotype. The decreased expression of CD11c, however, was recovered by culturing them with granulocyte-macrophage colony-stimulating factor, while they acquired a mature phenotype qby granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, interleukin-1alpha, or lipo-polysaccharide. Macrophage colony-stimulating factor-induced Langerhans cells could stimulate allogeneic T cells. Interestingly, we could keep the growth and immature phenotypes of macrophage colony-stimulating factor-induced Langerhans cells for at least 28 d of culture. These studies demonstrated that macrophage colony-stimulating factor in cooperation with transforming growth factor-beta1 could induce Langerhans cell development from hematopoietic progenitor cells in vitro without granulocyte-macrophage colony-stimulating factor, which suggests the possibility that macrophage colony-stimulating factor plays a part in the Langerhans cell development in vivo. In addition, the culture using macrophage colony-stimulating factor presents a novel culture system to enable a large-scale and long-term culture of immature Langerhans cells.

Antigens, CD34↗
PubMed2006

Bovine natural killer cells restrict the replication of Mycobacterium bovis in bovine macrophages and enhance IL-12 release by infected macrophages.

In this contribution, the impact of bovine natural killer (NK) cells on resistance to bovine tuberculosis was studied, using a monoclonal antibody against bovine NKp46. NK cells cultured with M. bovis-infected macrophages, but not control uninfected macrophages, proliferated and released IFN-gamma. Blood monocyte-derived macrophages were infected with virulent M. bovis, and growth of intra-macrophage bacteria was monitored by incorporation of tritiated uracil. Co-culturing infected macrophages with autologous NK cells significantly reduced the intracellular bacterial growth. Stimulation of NK cells with interleukin-2 (IL-2) enhanced further the capacity of these cells to reduce M. bovis replication in infected macrophages. NK cells from both BCG vaccinated and unvaccinated animals mediated this intra-macrophage growth restriction at similar levels. The ability of NK cells to reduce bacterial growth was independent of the release of IFN-gamma, as blocking IFN-gamma with an antibody in vitro did not affect intra-macrophage bacterial growth. NK cells reduced bacterial growth and also increased macrophage release of interleukin-12 (IL-12) and nitric oxide (NO) production by M. bovis-infected macrophages. Neutralizing NO production by macrophages in vitro with mono-methyl-l-arginine (MMLA) did not abrogate the ability of NK cells to decrease bacterial growth in infected macrophages. Reduction of mycobacterial intra-macrophage growth by NK cells was dependent on direct contact between NK cells and infected macrophages. Supernatants from NK cells failed to impact significantly on M. bovis replication in infected macrophages. The reduction in bacterial growth in macrophages correlated with the induction of an apoptosis program in infected macrophages. Cell death occurred at a similar rate in infected macrophages, exposed to NK cells or not. We conclude that bovine NK cells are stimulated by and release IFN-gamma in response to infected cells and reduce M. bovis growth in infected macrophages by an unclear mechanism, and are potentially involved in innate resistance of cattle to tuberculosis.

Animals↗
PubMed1983

Tumor-associated macrophages of mouse mammary tumors. II. Differential distribution of macrophages from metastatic and nonmetastatic tumors.

Macrophage subpopulations were isolated by counterflow centrifugal elutriation from a number of closely related mammary tumors originally derived from a single spontaneous tumor in a BALB/cfC3H mouse. Each tumor line had its own distinct characteristics with regard to tumor cell distribution, macrophage size (density), macrophage content, and macrophage distribution. Although there is no correlation with the metastatic potential of the tumors for the first three characteristics listed, distinct differences are apparent between metastatic and nonmetastatic tumors in macrophage distribution into the elutriated fractions. The distribution of the tumor-associated macrophages was shifted toward the later fractions in the metastatic tumors (lines 66 and 410.4), with approximately 40% more macrophages in fractions 3 and 4 than in those fractions from the nonmetastatic tumors (lines 67 and 168). The levels of three ectoenzymes, leucine aminopeptidase (LAP), alkaline phosphodiesterase I (APD), and 5' nucleotidase (5'N) were determined for macrophages from the elutriated fractions as well as for the total tumor digest. No significant differences were observed in absolute levels of either LAP or APD between most of the fractions from the different tumor lines. Differences were seen between the fractions in levels of 5'N among the lines and in ADP levels between lines 66 and 168 from the total tumor digest. Striking differences in ectoenzyme levels were apparent when the activity was normalized to macrophage surface area: macrophages from line 66 tumors were 3- to 17-fold higher in their LAP concentrations than were macrophages from either 67 or 168 tumors. Each tumor line had a unique and reproducible pattern of macrophage-associated prostaglandin E (PGE) synthesis. The three nonmetastatic tumor lines showed peak PGE levels in fraction three with lower levels in fraction 2, whereas the highly metastatic tumor yielded more active macrophages in fraction 2 vs fraction 3. Changes in PGE levels were associated with differing ectoenzyme levels. Macrophages in fraction 3 from metastatic tumors were enriched for populations with high LAP activity and low PGE levels. Conversely, macrophages from nonmetastatic tumors exhibited lower LAP activity in fraction 3 vs 2 and increasing PGE levels. Thus, differences between metastatic and nonmetastatic mammary tumors were seen in 1) distribution of macrophages in the elutriation fractions, 2) size of infiltrating macrophages, 3) macrophage ectoenzyme concentrations, and 4) macrophage-associated PGE levels.

Animals↗
PubMed1986

Induction of tumor cell resistance to macrophage-mediated lysis by preexposure to non-activated macrophages.

Thioglycollate-elicited peritoneal exudate (non-activated) macrophages do not lyse tumor cells and in contrast to activated macrophages bind less target cells. However, a non-lethal encounter of tumor cells with non-activated macrophages resulted in a pronounced effect on the subsequent tumor cell binding to and lysis by activated macrophages. Our results have shown that binding of tumor cells by non-activated macrophages was Ca2+ and temperature dependent; had a requirement for a Pronase-sensitive structure on macrophage surface membranes; was saturable; and was 2-3X less than that observed for activated macrophages. Experiments were conducted in which syngeneic tumor cells were incubated with a monolayer of non-activated macrophages and then assayed for selective binding and sensitivity to lysis. The important observations were that as a result of a 3-hr incubation with non-activated macrophages at an EC: TC ratio of 5:1 there was an increase in the number of tumor cells that bound to both activated and non-activated macrophages; a loss of selective binding in which the ratio of tumor cells bound to activated/non-activated macrophages (normally greater than 2) was lowered to 1.0; and a concomitant decrease in the susceptibility of tumor cells to macrophage-mediated cytolysis. The induction of tumor cell resistance to macrophage kill required an exposure to an excess number of non-activated macrophages, was reversible upon culturing with or without macrophages for 24 hr and required cell-cell contact. Our results reinforce the importance of selective binding between tumor cells and activated macrophages as an initial phase in tumor cell killing and also illustrates an active role for non-activated macrophages in vivo in allowing tumor cells to escape the immune surveillance by activated macrophages.

Animals↗
PubMed2003

Increased apoptotic neutrophils and macrophages and impaired macrophage phagocytic clearance of apoptotic neutrophils in systemic lupus erythematosus.

OBJECTIVE: To evaluate whether patients with systemic lupus erythematosus (SLE) have a higher rate of apoptosis in and secondary necrosis of polymorphonuclear neutrophils (PMNs) and macrophages compared with controls; to compare the rate of macrophage phagocytic clearance of apoptotic PMNs in patients with SLE and healthy controls; to evaluate whether in vitro PMN and macrophage apoptosis and secondary necrosis, and the ability of macrophages to phagocytose apoptotic bodies, are correlated with lupus disease activity; and to determine whether macrophage clearance of apoptotic bodies in patients with SLE and normal controls is related to certain serum factors. METHODS: Thirty-six patients with SLE and 18 healthy, nonsmoking volunteers were studied. PMNs and monocytes were isolated from fresh blood and cultured in the presence of different sources of serum. Apoptotic PMNs and macrophages were examined by annexin V binding and morphology on May-Giemsa-stained cytopreparations, at different time points. The presence of secondary necrotic PMNs and macrophages was verified by staining with trypan blue. Macrophage phagocytosis of apoptotic PMNs was measured using a coded, observer-blinded, microscopically quantified phagocytosis assay. Cells were cultured in the presence of serum obtained from healthy subjects or from patients with SLE. RESULTS: At 5 and 24 hours, the percentage of apoptotic PMNs from patients with SLE was significantly higher than that of PMNs from healthy subjects. At 24 and 48 hours, the percentage of secondary necrotic PMNs from patients with SLE was also significantly higher than the percentage of necrotic PMNs from controls. Serum from patients with SLE accelerated the rate of apoptosis in and secondary necrosis of PMNs from healthy subjects. Macrophages from SLE patients were less capable of phagocytosing apoptotic PMNs compared with macrophages obtained from controls. Macrophages from patients with active SLE were less capable of phagocytosing apoptotic PMNs than were macrophages from patients with inactive SLE, but the difference was not statistically significant. The percentage of phagocytosis of apoptotic PMNs by macrophages from SLE patients correlated negatively with the SLE Disease Activity Index, serum levels of anti-double-stranded DNA, and the erythrocyte sedimentation rate, and correlated positively with serum levels of C3, C4, and albumin, the hemoglobin level, and the leukocyte count. Serum from SLE patients not only significantly increased macrophage apoptosis in cells from healthy subjects but also remarkably down-regulated the clearance of apoptotic PMNs by macrophages from healthy subjects. In contrast, serum from healthy subjects significantly increased phagocytosis of apoptotic PMNs by macrophages from SLE patients. CONCLUSION: The observed increase of apoptotic PMNs and macrophages and the poor ability of macrophages from patients with SLE to phagocytose apoptotic bodies may indicate an impaired clearance mechanism, which may be mediated by factors in a patient's serum.

Adolescent↗
PubMed1981

Different macrophage populations distinguished by means of fluorescent polysaccharides. Recognition and properties of marginal-zone macrophages.

Fluorescent conjugates of hydroxyethyl (OEt) starch of Ficoll are selectively ingested and retained in vivo by spleen marginal-zone (MZ) and lymph node marginal-sinus macrophages of mice, whereas similar conjugates of type 3 pneumococcal capsular polysaccharide (SIII) are generally retained by macrophages (Kupffer cells, histiocytes, macrophages of spleen, lymph nodes, bone marrow and peritoneal cavity). MZ and other macrophages are readily identifiable by fluorescence after injection in vivo of OEt starch and SIII labeled with tetraethylrhodamine isothiocyanate and fluorescein isothiocyanate. Collagenase digestion was required for recovery of intact MZ macrophages from spleen in single cell suspensions and for maximum yields of other macrophages. MZ macrophages are larger and morphologically distinct from other macrophages, but resemble them in respect of EA, EAC receptors and acid phosphates and nonspecific esterase content and are equally radio-resistant. The appear normal in CBA/N nude and in beige mice. Freshly isolated MZ macrophages in suspension have adherent lymphocytes, dispersible by EDTA treatment, with B but not T cell markers. It is suggested that selective adherence to MZ macrophages is a factor in determining B cell traffic. MZ macrophages did not have demonstrable surface I-A or I-EC antigens. Only 4--8% of other spleen macrophages freshly isolated by collagenase treatment expressed I-A in the same preparation, whereas 35% of other cells (lymphocytes and blasts) reacted with monoclonal anti-I-A and anti-I-EC. After adherence to glass or plastic, 40% or more red-pulp, but not MZ macrophages, became I-A-positive. When taken from mice recently restimulated with sheep erythrocytes, half the red-pulp macrophages expressed I-A even before adherence. The relation of MZ to other macrophages is not known. However, their properties are consistent with the demonstrated ability of thymus-independent antigens selectively taken up by these cells to elicit long-lasting IgM antibody responses by direct interaction with B cells. The unexpected observation that only a small proportion of spleen macrophages freshly isolated from unstimulated mice had detectable surface I-A, but that this proportion was much increased after attachment to plastic, is discussed in relation to the possibility that macrophages do not express surface Ia antigens unless they have been stimulated.

Animals↗
PubMed1995

Replication of macrophage-tropic and T-cell-tropic strains of human immunodeficiency virus type 1 is augmented by macrophage-endothelial cell contact.

Macrophages perform a central role in the pathogenesis of human immunodeficiency virus type 1 (HIV-1) infection and have been implicated as the cell type most prominent in the development of central nervous system impairment. In this study, we evaluated the effect of interaction between macrophages and endothelial cells on HIV-1 replication. Upregulation of HIV-1 replication was consistently observed in monocyte-derived macrophages (hereafter called macrophages) cocultured with either umbilical vein endothelial cells or brain microvascular endothelial cells. HIV-1 p24 antigen production of laboratory-adapted strains and patient-derived isolates was increased 2- to 1,000-fold in macrophage-endothelial cocultures, with little or no detectable replication in cultures containing endothelial cells only. The upregulation of HIV-1 in macrophage-endothelial cocultures was observed not only for viruses with the non-syncytium-inducing, macrophage-tropic phenotype but also for viruses previously characterized as syncytium inducing and T-cell tropic. In contrast, cocultures of macrophages with glioblastoma, astrocytoma, cortical neuronal, fibroblast, and placental cells failed to increase HIV-1 replication. Enhancement of HIV-1 replication in macrophage-endothelial cocultures required cell-to-cell contact; conditioned media from endothelial cells or macrophage-endothelial cocultures failed to augment HIV-1 replication in macrophages. Additionally, antibody to leukocyte function-associated antigen (LFA-1), a macrophage-endothelial cell adhesion molecule, inhibited the enhanced HIV-1 replication in macrophage-endothelial cell cocultures. Thus, these data indicate that macrophage-endothelial cell contact enhances HIV-1 replication in macrophages for both macrophage-tropic and previously characterized T-cell-tropic strains and that antibody against LFA-1 can block the necessary cell-to-cell interaction required for the observed upregulation. These findings may have important implications for understanding the ability of HIV-1 to replicate efficiently in tissue macrophages, including those in the brain and at the blood-brain barrier.

Antibodies, Monoclonal↗
PubMed1971

Macrophage-melanoma cell heterokaryons. 3. The activation of macrophage DNA synthesis. Studies with inhibitors of protein synthesis and with synchronized melanoma cells.

Dormant macrophage nuclei initiate DNA synthesis 2-3 hr after fusion of macrophages with exponentially growing melanoma cells. Cycloheximide treatment (1-5 microg/ml) of heterokaryons during the preceding lag period inhibits the initiation of macrophage DNA synthesis, in a reversible fashion. Each type of cell was also treated with streptovitacin A, an irreversible inhibitor of protein synthesis. Pretreatment of the melanoma cells (0.5-2 microg/ml), 1 hr before fusion, inhibited the induction of macrophage DNA synthesis in heterokaryons, whereas pretreatment of macrophages (1-20 microg/ml) had no effect. Melanoma cell pretreatment reduced the incorporation of leucine-(3)H into the cytoplasm and nuclei of heterokaryons, whereas macrophage pretreatment had no effect. These experiments suggested that melanoma proteins played an important role in the initiation of macrophage DNA synthesis. The relationship between the melanoma cell cycle and macrophage DNA synthesis was studied with synchronous melanoma cells. If the melanoma cells were in S phase at the time of fusion, macrophage DNA synthesis occurred 2 hr later. However, the fusion of melanoma cells in G(1) delayed macrophage DNA synthesis until the melanoma nuclei had entered S. Experiments with actinomycin and cycloheximide showed that RNA and protein, essential to achieve DNA synthesis in the macrophage nucleus, were made during late G(1) as well as S. Melanoma cells and macrophages differ in their radiolabeled acid-soluble products after incubation in thymidine-(3)H. Thymidine taken up by the macrophage remained unphosphorylated, whereas it was recovered mainly as thymidine triphosphate from melanoma cells. These findings, as well as those reported previously, suggest that the melanoma cell provides the RNA, protein, and precursors which initiate macrophage DNA synthesis. In the absence of a requirement for new macrophage RNA and protein synthesis, other changes must be responsible for the 2 hr delay in DNA synthesis. These may involve physical changes in DNA, associated with swelling, as well as the transport of melanoma products into the macrophage nucleus.

Animals↗
PubMed2006

Constitutive receptor-independent low density lipoprotein uptake and cholesterol accumulation by macrophages differentiated from human monocytes with macrophage-colony-stimulating factor (M-CSF).

Recently, we have shown that macrophage uptake of low density lipoprotein (LDL) and cholesterol accumulation can occur by nonreceptor mediated fluid-phase macropinocytosis when macrophages are differentiated from human monocytes in human serum and the macrophages are activated by stimulation of protein kinase C (Kruth, H. S., Jones, N. L., Huang, W., Zhao, B., Ishii, I., Chang, J., Combs, C. A., Malide, D., and Zhang, W. Y. (2005) J. Biol. Chem. 280, 2352-2360). Differentiation of human monocytes in human serum produces a distinct macrophage phenotype. In this study, we examined the effect on LDL uptake of an alternative macrophage differentiation phenotype. Differentiation of macrophages from human monocytes in fetal bovine serum with macrophage-colony-stimulating factor (M-CSF) produced a macrophage phenotype demonstrating constitutive fluid-phase uptake of native LDL leading to macrophage cholesterol accumulation. Fluid-phase endocytosis of LDL by M-CSF human macrophages showed non-saturable uptake of LDL that did not down-regulate over 48 h. LDL uptake was mediated by continuous actin-dependent macropinocytosis of LDL by these M-CSF-differentiated macrophages. M-CSF is a cytokine present within atherosclerotic lesions. Thus, macropinocytosis of LDL by macrophages differentiated from monocytes under the influence of M-CSF is a plausible mechanism to account for macrophage foam cell formation in atherosclerotic lesions. This mechanism of macrophage foam cell formation does not depend on LDL modification or macrophage receptors.

Cell Differentiation↗
PubMed2000

Membrane surface of Mycobacterium microti-infected macrophages antigenically differs from that of uninfected macrophages.

Identification of the antigenic changes in mycobacteria-infected macrophage may be important in understanding the mechanisms responsible for the intracellular survival of the bacteria. In the present study, Mycobacterium microti-infected macrophages were utilized to investigate the possibility of differentiating the infected cells from normal cells, based on the antigenic changes occurring in the membranes. Antisera were generated against bacterial extract, heat-killed bacteria and crude preparation of M. microti-infected homologous macrophage membrane. The reactivity of these antisera, towards in vitro infected macrophages, was compared by flow cytometry. Unlike anti-bacterial extract antiserum or anti-heat-killed bacterial antiserum, anti-infected macrophage membrane antiserum reacted with infected macrophage surface. This reactivity increased with the increase in post-infection time. However, it was not observed with uninfected macrophages, PMA- or lipopolysaccharide-activated macrophages and those harboring Mycobacterium tuberculosis H37Ra, heat-killed M. microti and Leishmania donovani. Interestingly, anti-infected macrophage membrane antiserum identified a 63-kDa antigen in M. microti-infected macrophage membranes which was not present in the membranes of normal macrophages, activated macrophages and of those infected with M. tuberculosis H37Ra, heat-killed M. microti and L. donovani. Thus, membranes of M. microti-infected macrophages differ antigenically from those of the normal macrophages and infected homologous macrophage membrane antiserum provides a useful tool in studying such changes.

Animals↗
PubMed1995

Macrophage distribution in decidual tissue from early implantation to the periparturient period in mice as defined by the macrophage differentiation antigens F4/80, macrosialin and the type 3 complement receptor.

Antibodies to differentiation markers have made it possible to identify macrophages in murine tissues. Macrophages are potent mediators of immunological reactions and it has been proposed that they are pivotal cells at the maternal-fetal interface. Studies of macrophage distribution in murine decidual tissue have provided conflicting evidence for and against the presence of significant numbers of macrophages at the maternal-fetal interface. The study described here used three independent macrophage differentiation antigens to examine the macrophage distribution in decidual tissue from day 6 to day 19 of pregnancy. Macrophage distribution was defined initially using a polyclonal antiserum to the plasma membrane differentiation antigen F4/80. Macrophages were virtually absent from antimesometrial decidual tissue until degenerating tissue was invaded by macrophages from about day 15. The resident population of macrophages in the mesometrial stroma was retained when this area decidualized but these cells did not survive beyond day 13. Mesometrial decidual tissue was virtually devoid of macrophages after this time. The metrial gland contained many macrophages until degeneration set in, but few were seen by day 15 of pregnancy. These distributions were confirmed using monoclonal antibodies (mAb) to F4/80, macrosialin, a monocyte- and macrophage-specific membrane sialoprotein (mAb FA/11), and the leucocyte beta 2-integrin CR3 (CD11b/CD18; Mac-1), which is expressed on neutrophils as well as monocytes and some tissue macrophages. CR3+, F4/80- and FA/11- neutrophils were found to be more widely distributed in decidual tissue than were F4/80+ or FA/11+ macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Murine macrophage scavenger receptor: in vivo expression and function as receptor for macrophage adhesion in lymphoid and non-lymphoid organs.

Macrophage scavenger receptors are trimeric integral membrane glycoproteins which have been implicated in various macrophage functions including uptake of oxidized lipoprotein and the serum-dependent, divalent cation-independent adhesion of macrophages to tissue culture-treated plastic. In this study we have used a recently defined monoclonal antibody (2F8) which recognizes murine macrophage scavenger receptor, to explore its expression in lymphoid and non-lymphoid organs of the normal adult. Scavenger receptor was detected in the red pulp and marginal zone of normal adult mouse spleen, medulla of the thymus and subcapsular region of lymph nodes. Kupffer cells in the liver, alveolar macrophages in the lung and lamina propria macrophages in the gut all reacted with 2F8 monoclonal antibody. The antigen was not detected on any non-macrophage cells, with the exception of sinusoidal endothelial cells in the liver. In the spleen, lymph node and liver, scavenger receptor antigen expression was associated specifically with phagocytic cells which had taken up colloidal carbon. To examine macrophage adhesion in a context relevant to the interactions occurring within lymphoid and non-lymphoid organs, and the contribution of macrophage scavenger receptor to this adhesion, we designed an assay of macrophage adhesion to frozen tissue sections. Adhesion to most tissues was high and uniform in the absence of any chelating agents. The chelation of Ca2+ and Mg2+ revealed specific patterns of macrophage adhesion in lymphoid and non-lymphoid organs which was completely inhibited by 2F8. The ability of this antibody to block the EDTA-resistant adhesion correlated with tissue expression of the antigen in some tissues. Unlike adhesion to tissue culture-treated plastic, macrophage scavenger receptor-dependent adhesion of macrophages to frozen tissue sections did not exhibit an absolute requirement for exogenous fetal bovine serum indicating the presence of an endogenous ligand for scavenger receptor within the tissues. We propose that macrophage scavenger receptor is a candidate homing or retention molecule for macrophage localization within ligand-rich tissues.

Animals↗
PubMed1987

Macrophages, macrophage foam cells, and eccentric intimal thickening in the coronary arteries of young children.

We surveyed the incidence and location of macrophages and macrophage foam cells in the coronary artery intima of 63 children that died in the first 5 years of life. We related the data on macrophages and macrophage foam cells to intimal smooth muscle cells and to measurements of intima:media area and thickness. All morphometric data were obtained from coronary arteries that were fixed by perfusion with glutaraldehyde under pressure, embedded in Maraglas, and cut into 1-micron cross-sections, and 65-nm fine sections. Coronary artery intima was always thicker (eccentric thickening) at bifurcations in the half of the circumference opposite to the flow divider. This was true for both male and female children. The remaining part of the coronary artery intima was less thick (diffuse thickening). Both types of intimal thickening were composed of an inner layer in which glycosaminoglycan ground substance predominated and a deeper musculoelastic layer. Fifty-nine children (94%) had intimal macrophages. Twenty children also had macrophage foam cells. Of 33 children aged to 8 months, 15 (45%) had macrophage foam cells. Of the 30 children older than 8 months, 5 (17%) had macrophage foam cells. Macrophages and macrophage foam cells occurred in the GAG-rich layer of the intima as isolated cells. In 5 infants macrophage foam cells occurred also as clusters of many cells. Macrophages were more numerous in cases that also had macrophage foam cells. Macrophages were 6 times, and macrophage foam cells 5 times more numerous in eccentric intimal thickening than in diffuse intimal thickening.

Arteriosclerosis↗
PubMed1989

Intracellular survival of wild-type Salmonella typhimurium and macrophage-sensitive mutants in diverse populations of macrophages.

Salmonella typhimurium survives within macrophages and causes a fatal infection in susceptible strains of mice. A number of S. typhimurium mutants that contain Tn10 insertions in genes which are necessary for survival within the macrophage have been isolated. To demonstrate the importance of each gene in intracellular survival, the mutations were transduced into a smooth-strain background and the ability to survive intracellularly was assayed in five different populations of macrophages. The majority of the original macrophage-sensitive mutants retained the macrophage-sensitive phenotype in the smooth-strain background. The ability to survive or grow within macrophages varied with both the source of macrophages and the individual mutants. S. typhimurium grew best in the macrophage-like cell line J774, survived at moderate levels in splenic and bone marrow-derived macrophages, and was killed most efficiently in peritoneal macrophages. Macrophage-sensitive mutants transduced into a smooth background were also less virulent than the parent, with a 50% lethal dose of 2 to 5 logs greater than that of the parental strain. These experiments demonstrate that survival of S. typhimurium within macrophages varies with the source of cells, with a distinct ability to survive in macrophages from mouse spleens, where S. typhimurium grows rapidly. These experiments also demonstrate the heterogeneity in intracellular survival among the various macrophage-sensitive mutants, which may reflect the relative importance of the individual mutated genes in survival within macrophages.

Animals↗
PubMed1988

Pulmonary intravascular macrophages metabolize arachidonic acid in vitro. Comparison with alveolar macrophages.

Pulmonary intravascular macrophages are a recently identified component of the pulmonary mononuclear phagocyte system. It has been shown that alveolar macrophages are capable of metabolizing arachidonic acid (AA) to its biologically active inflammatory metabolites via the lipoxygenase and cyclooxygenase pathways. In this study, we have compared the ability of swine intravascular macrophages and alveolar macrophages to metabolize AA in vitro. Alveolar macrophages attached to a plastic substrate produced at least five identified AA metabolites including prostaglandin (PG)F2 alpha, hydroxyheptadecatrienoic acid (HHT), 5-hydroxyeicosatetraenoic acid (HETE), 12-HETE, and 15-HETE. In contrast, adherent intravascular macrophages produced eight identified metabolites including thromboxane (TX)B2, PGF2 alpha, PGD2, PGE2, HHT, 5-HETE, 12-HETE, and 15-HETE. The major lipoxygenase metabolite produced by both macrophage types was 5-HETE. The major cyclooxygenase metabolite produced by alveolar macrophages was PGF2 alpha, whereas the major metabolite produced by intravascular macrophages was HHT. Both macrophage populations treated with calcium ionophore (A23187) exhibited increased production of PGs, TXB2, leukotriene (LT)B4, 5-HETE, 12-HETE, and 15-HETE, but the most striking increase occurred in metabolism through the lipoxygenase pathway. The major lipoxygenase metabolite generated by ionophore-stimulated macrophages was 5-HETE, and in intravascular macrophages 12-HETE was also produced. Preincubation of macrophages with indomethacin and nordihydroguaiaretic acid attenuated the yield of cyclooxygenase metabolites and lipoxygenase metabolites, respectively. Studies of leukotriene formation demonstrated that both macrophage types produce LTC4 and LTB4 from the leukotriene precursor LTA4. Thus, we show that the pulmonary intravascular macrophage is capable of metabolizing AA and LTA4 to their inflammatory and vasoactive metabolites by the cyclooxygenase and lipoxygenase pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1975

Interactions between actin, myosin, and an actin-binding protein from rabbit alveolar macrophages. Alveolar macrophage myosin Mg-2+-adenosine triphosphatase requires a cofactor for activation by actin.

The interactions were analyzed between actin, myosin, and a recently discovered high molecular weight actin-binding protein (Hartwig, J. H., and Stossel, T. P. (1975) J. Biol Chem.250,5696-5705) of rabbit alveolar macrophages. Purified rabbit alveolar macrophage or rabbit skeletal muscle F-actins did not activate the Mg2+ATPase activity of purified rabbit alveolar macrophage myosin unless an additional cofactor, partially purified from macrophage extracts, was added. The Mg2+ATPase activity of cofactor-activated macrophage actomyosin was as high as 0.6 mumol of Pi/mg of myosin protein/min at 37 degrees. The macrophage cofactor increased the Mg2+ATPase activity of rabbit skeletal muscle actomyosin, and calcium regulated the Mg2+ATPase activity of cofactor-activited muscle actomyosin in the presence of muscle troponins and tropomyosin. However, the Mg2+ATPase activity of macrophage actomyosin in the presence of the cofactor was inhibited by muscle control proteins, both in the presence and absence of calcium. The Mg2+ATPase activity of the macrophage actomyosin plus cofactor, whether assembled from purified components or studied in a complex collected from crude macrophage extracts, was not influenced by the presence of absence of calcium ions. Therefore, as described for Acanthamoeba castellanii myosin (Pollard, T. D., and Korn, E. D. (1973) J. Biol. Chem. 248, 4691-4697), rabbit alveolar macrophage myosin requires a cofactor for activation of its Mg2+ATPase activity by F-actin; and no evidence was found for participation of calcium ions in the regulation of this activity. In macrophage extracts containing 0.34 M sucrose, 0.5 mM ATP, and 0.05 M KCl at pH 7.0,the actin-binding protein bound F-actin into bundles with interconnecting bridges. Purified macrophage actin-binding protein in 0.1 M KCl at pH 7.0 also bound purified macrophage F-actin into filament bundles. Macrophage myosin bound to F-actin in the absence but not the presence of Mg2+ATP, but the actin-binding protein did not bind to macrophage myosin in either the presence or absence of Mg2+ATP.

Actins↗