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 235 records · Page 13Linked to original sources
PubMed1984

Macrophages in resistance to rickettsial infections: protection against lethal Rickettsia tsutsugamushi infections by treatment of mice with macrophage-activating agents.

Peritoneal macrophages of BALB/c and C3H/HeN mice activated in vivo by intraperitoneal inoculation of viable Mycobacterium bovis strain BCG or the nonliving macrophage-activating agent Propionibacterium acnes (Corynebacterium parvum), were resistant to infection with Rickettsia tsutsugamushi, and they killed bacteria that did gain entry into the intracellular environment of these cells. This macrophage resistance to infection and intracellular destruction of rickettsiae was dependent upon development of an immune response to the activating agents, since macrophages elicited by sterile inflammatory agents failed to display either microbicidal activity unless cells were exposed to factors present in lymphokine-rich culture fluids from antigen or mitogen stimulated spleen cells (LK) in vitro. C3H/HeN mice that had been treated with activating agents, but not sterile inflammatory irritants, also survived intraperitoneal inoculation of up to 10(4) R. tsutsugamushi. This nonspecific protection required the chronic presence of activated macrophages: acute immune response induced by intraperitoneal injection of PPD into mice inoculated intradermally with BCG, or intraperitoneal inoculation of conconavalin A, were not sufficient to induce survival of rickettsial disease, although macrophages from these animals were activated to kill rickettsiae at the time of challenge. The critical nature of activated macrophages in nonspecific protection against rickettsial infection was demonstrated with the macrophage-defective C3H/HeJ mice. These mice are equally as susceptible as C3H/HeN mice to intraperitoneal inoculation of R. tsutsugamushi, but do not develop activated macrophages in response to BCG infection, and are not protected against lethal rickettsial challenge following BCG treatment.

Animals↗
PubMed1998

Expression of macrophage-derived chemokine (MDC) mRNA in macrophages is enhanced by interleukin-1beta, tumor necrosis factor alpha, and lipopolysaccharide.

A cDNA encoding the C-C chemokine MDC was isolated from a human macrophage cDNA library by differential hybridization using monocyte- and macrophage-specific cDNA probes. During monocyte to macrophage differentiation in vitro, MDC expression is first detected after 1 day of culturing and reaches maximum levels after 6 days when macrophages have fully matured, as judged from the expression of known macrophage marker genes. Exposure of macrophages to lipopolysaccharide (LPS) results in a dose-dependent increase in MDC mRNA levels, with maximum induction occurring after 6-8 h, whereas expression levels of macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-2, interleukin-1beta (IL-1beta), and tumor necrosis factor alpha (TNF-alpha) respond much faster to LPS. Furthermore, MDC expression in macrophages is enhanced by the inflammatory mediators TNF-alpha and IL-1beta. Similar to other TNF-alpha/IL-1beta-inducible genes, costimulation of macrophages with both cytokines leads to higher MDC expression levels than stimulation with a single cytokine. By contrast, both resting and activated monocytes do not express MDC mRNA.

Chemokine CCL22↗
PubMed1991

Glycosaminoglycan profile of peritoneal and bone marrow-derived macrophages. Changes associated with macrophage activation.

1. We have analysed the glycosaminoglycan patterns of peritoneal and bone marrow-derived macrophages obtained from four different mouse strains which are resistant (A/J) or susceptible (BALB/c, DBA and C-57) to murine hepatitis virus type 3 (MHV3) infection. The glycosaminoglycans were biosynthetically labelled by exposing the macrophages to 35S-sulphate. The medium and cell fractions were collected and the 35S-glycosaminoglycans formed were identified by a combination of agarose gel electrophoresis and enzymatic degradation with bacterial mucopolysaccharidases. 2. Both peritoneal and bone marrow-derived macrophages synthesize and secrete a mixture of dermatan sulphate, heparan sulphate and chondroitin sulphate. Dermatan sulphate is the main glycosaminoglycan and most of the synthesized glycosaminoglycans are released to the culture medium. 3. The glycosaminoglycan patterns vary depending on the macrophage source. Bone marrow-derived cells synthesize glycosaminoglycans at lower rates, release a lower glycosaminoglycan percentage to the culture medium and express higher amounts of heparan sulphate in comparison with their peritoneal counterparts. Furthermore, LPS-induced activation leads to an increased glycosaminoglycan expression in bone marrow-derived macrophages and to a decrease in 35S-glycosaminoglycans of peritoneal macrophages from BALB/c, A/J and C-57 mice. 4. We have not established any correlation between macrophage glycosaminoglycans and resistance to MHV3 infection, since the glycosaminoglycan patterns of resistant (A/J) and susceptible (BALB/c, DBA and C-57) mouse macrophages are similar. Furthermore, the in vitro infection of both control and LPS-activated peritoneal macrophages with MHV3 did not cause any changes in the expression of glycosaminoglycans.

Animals↗
PubMed1999

Activation of macrophage tumoricidal activity by photodynamic treatment in vitro--indirect activation of macrophages by photodynamically killed tumor cells.

Macrophages constitute a major part of natural tumor defense by their capacity to destroy selectively a broad range of tumor types upon specific activation. In the last couple of years, these cells have also been implicated as effector cells in the destruction of tumors by photodynamic therapy. In the present work, the potential role of macrophage-mediated tumor cytotoxicity after photodynamic treatment in vitro has been investigated with respect to photodynamic activation of macrophages for tumoricidal effector functions. Our data show that photodynamic treatment of highly pure murine bone-marrow-derived macrophages with the hematoporphyrin derivative Photosan-3 does not result in activation of these cells for cytotoxicity against YAC-1 tumor cells or secretion of tumor necrosis factor and nitric oxide, irrespective of co-stimulation with interferon-gamma, a potent priming agent for macrophage antitumoral activity. On the contrary, treatment with higher photosensitizer doses is found to reduce markedly the viability of the macrophage effector cells. Thus, these results do not lend any support to the hypothesis of direct macrophage activation by photodynamic treatment. However, macrophages are found to be activated for tumoricidal effector functions indirectly by photodynamically killed tumor cells, in a way reminiscent of phagocytosis-inducing stimuli. It is thus suggested that recognition and phagocytosis of photodynamically destroyed tumor cells constitutes the major signal for local activation of macrophages in photodynamically treated tumor tissues, which may be crucial for final, specific eradication by the immune system of tumor cells surviving photodynamic treatment.

Animals↗
PubMed2000

Induction of potent antitumor response by vaccination with tumor lysate-pulsed macrophages engineered to secrete macrophage colony-stimulating factor and interferon-gamma.

Adoptive transfer of activated macrophages, being both effector cells and antigen-presenting cells, represents a promising approach to immunotherapy of cancer. In order to get activated macrophages with increased antitumor potential, in the present study, murine peritoneal macrophages were transduced with human macrophage colony-stimulating factor (M-CSF) and murine interferon-gamma (IFNgamma) by recombinant adenovirus infection. The results demonstrate that M-CSF and IFNgamma gene-modified macrophages exhibited higher expression of MHC-II, B7.1 and ICAM-1, increased antigen-presenting activity and cytotoxicity. It was also shown that they secreted more tumor necrosis factor, interleukin-1 and nitric oxide. In vivo experiments showed that in previously initiated murine pulmonary metastatic melanoma, tumor lysate-pulsed, M-CSF and IFNgamma gene-modified macrophages elicited more potent antitumor effects than tumor lysate pulsed M-CSF or IFNgamma gene-modified macrophages. Cytotoxic T lymphocyte (CTL) activity, IFNgamma and tumor-necrosis factor production of the splenocytes increased significantly in mice after intravenous injection of the gene-modified macrophages. M-CSF and IFNgamma gene-modified macrophages may act as activated effector and antigen-presenting cells, thus eliciting a more potent antitumor response.

Animals↗
PubMed2000

Macrophage colony-stimulating factor rapidly enhances beta-migrating very low density lipoprotein metabolism in macrophages through activation of a Gi/o protein signaling pathway.

Previous studies have examined lipoprotein metabolism by macrophages following prolonged exposure (>24 h) to macrophage colony-stimulating factor (M-CSF). Because M-CSF activates several signaling pathways that could rapidly affect lipoprotein metabolism, we examined whether acute exposure of macrophages to M-CSF alters the metabolism of either native or modified lipoproteins. Acute incubation of cultured J774 macrophages and resident mouse peritoneal macrophages with M-CSF markedly enhanced low density lipoproteins (LDL) and beta-migrating very low density lipoproteins (beta-VLDL) stimulated cholesteryl [(3)H]oleate deposition. In parallel, M-CSF treatment increased the association and degradation of (125)I-labeled LDL or beta-VLDL without altering the amount of lipoprotein bound to the cell surface. The increase in LDL and beta-VLDL metabolism did not reflect a generalized effect on lipoprotein endocytosis and metabolism because M-CSF did not alter cholesterol deposition during incubation with acetylated LDL. Moreover, M-CSF did not augment beta-VLDL cholesterol deposition in macrophages from LDL receptor (-/-) mice, indicating that the effect of M-CSF was mediated by the LDL receptor. Incubation of macrophages with pertussis toxin, a specific inhibitor of G(i/o) protein signaling, had no effect on cholesterol deposition during incubation with beta-VLDL alone, but completely blocked the augmented response promoted by M-CSF. In addition, incubation of macrophages with the direct G(i/o) protein activator, mastoparan, mimicked the effect of M-CSF by enhancing cholesterol deposition in cells incubated with beta-VLDL, but not acetylated LDL. In summary, M-CSF rapidly enhances LDL receptor-mediated metabolism of native lipoproteins by macrophages through activation of a G(i/o) protein signaling pathway. Together, these findings describe a novel pathway for regulating lipoprotein metabolism.

Androstadienes↗
PubMed2006

Inhibitor kappaB and nuclear factor kappaB in granulocyte-macrophage colony-stimulating factor antagonism of dexamethasone suppression of the macrophage response to Aspergillus fumigatus conidia.

BACKGROUND: The dexamethasone (DEX) immunosuppressive effect on macrophage killing activity and cytokine production in response to Aspergillus fumigatus conidia is antagonized by granulocyte-macrophage colony-stimulating factor (GM-CSF). The molecular mechanism is unknown. We postulated that this antagonism is mediated by inhibitor kappaB (I kappaB) induction by DEX and is opposed by acceleration of I kappaB degradation by GM-CSF with or without conidia stimulation, with corresponding effects on translocation and activation of nuclear factor kappa B (NF-kappaB). METHODS: We studied 2 types of cells, resident peritoneal macrophages from CD-1 mice and the murine macrophage RAW264.7 cell line. Cells were unstimulated or stimulated with conidia and simultaneously treated with DEX, GM-CSF, or DEX plus GM-CSF, for 2-4 hours. I kappaB degradation and NF-kappaB activation were assessed by Western blot. RESULTS: Macrophages stimulated with conidia alone increased NF-kappaB translocation. DEX increased I kappaB levels in cytoplasm and blocked translocation of NF-kappaB to the nucleus in unstimulated and conidia-stimulated macrophages. Conversely, GM-CSF decreased I kappaB levels. GM-CSF reversed the effect of DEX on I kappaB levels. NF-kappaB levels were minimal in DEX-treated macrophage nuclear extracts, compared with those from GM-CSF-treated and GM-CSF plus DEX-treated macrophages. CONCLUSION: GM-CSF can reverse the DEX immunosuppressive effect by enhancing I kappaB degradation and promoting NF-kappaB translocation. This would allow macrophage production of proinflammatory cytokines, facilitating resistance to aspergillosis.

Animals↗
PubMed1989

Macrophage activation decreases macrophage prostaglandin E2 release in experimental trauma.

Prostaglandin E2 (PGE2) derived from macrophages following trauma may contribute to trauma-induced immunosuppression. This study evaluated the effect of glucan, a macrophage-activating agent, on macrophage PGE2 release in a murine trauma model. ICR/HSD mice were administered D5W, glucan pre-trauma, or glucan post-trauma, and subjected to hindlimb crush and amputation injury. Splenic macrophages were isolated 24 hours following trauma, cultured (24 hrs), and macrophage PGE2 levels were determined. In-vitro marrow proliferation was assessed as a measure of immune function. Crush-amputation injury increased (184%) macrophage PGE2 release. In contrast, glucan administration (pre or post) reduced PGE2 levels in macrophage supernatants (71% and 85%, respectively). A 52% decrease in in-vitro bone marrow proliferation was observed following trauma. Glucan pre- or post-trauma eliminated the suppression of bone marrow proliferation. In conclusion, macrophage-activating immunomodulators may exert beneficial effects following trauma by: 1) reducing macrophage PGE2 synthesis and release; and 2) reducing traumatic suppression of bone marrow proliferation.

Amputation, Traumatic↗
PubMed1996

Decrease in scavenger receptor expression in human monocyte-derived macrophages treated with granulocyte macrophage colony-stimulating factor.

To determine whether scavenger receptors are susceptible to regulation by granulocyte macrophage colony-stimulating factor (GM-CSF), a macrophage-specific cytokine, human monocytes were differentiated into macrophages in the absence or presence of 20 U/mL GM-CSF. Binding, uptake, and degradation of acetylated LDL (Ac-LDL) and oxidized LDL (Ox-LDL) were measured. Treatment with GM-CSF resulted in a significant twofold to threefold decrease in the number of binding sites for Ac-LDL and Ox-LDL on the surface of macrophages without affecting the affinity of the receptor for these ligands. Competition experiments revealed that two binding sites were responsible for the recognition and uptake of Ac-LDL; one specific for Ac-LDL and one that recognized both Ac-LDL and Ox-LDL. No binding site specific for Ox-LDL could be detected in either control or GM-CSF-treated macrophages. Treatment of human monocyte-derived macrophages with GM-CSF resulted in a decrease of the Ac-LDL/Ox-LDL receptor but did not affect the binding site specific for Ac-LDL. Northern blot analysis showed that mRNA levels of both types I and II scavenger receptor were reduced in macrophages differentiated in the presence of GM-CSF. Human macrophages that were differentiated in the presence of GM-CSF accumulated approximately 50% fewer cholesteryl esters. Taken together, these results indicate that GM-CSF can downregulate both types I and II scavenger receptor in human monocyte-derived macrophages, which might have implications for foam cell formation.

Base Sequence↗
PubMed1996

Stimulation of macrophage DNA synthesis by polyanionic substances through binding to the macrophage scavenger receptor.

We previously demonstrated that ligands of macrophage scavenger receptors such as acetylated low density lipoprotein (LDL), oxidized LDL and advanced glycation-end products (AGE) of the Maillard reaction induce the growth of peritoneal exudate macrophages, and that the activity of AGE is inhibited by the presence of an antibody for granulocyte/macrophage colony-stimulating factor (GM-CSF). To evaluate the suggested role of the scavenger receptor in the induction of macrophage growth, we compared the effect of various polyanionic compounds which were reported to either have or not to have competent activity for the binding of acetylated LDL to scavenger receptors on macrophage DNA synthesis. Among the polyanions exhibiting such activity, polyguanilic acid (poly G) and dextran sulfate strongly augmented macrophage DNA synthesis, although they did not increase macrophage cell number. On the other hand, polyanions which are not ligands for the scavenger receptors did not show a significant augmenting effect, suggesting that the binding of polyanions to the scavenger receptor is important but not, by itself, sufficient. The augmentation of DNA synthesis in macrophages cultured with dextran sulfate or poly G was inhibited by the co-presence of anti-GM-CSF antibody, suggesting that the reaction is mediated by GM-CSF. However, dextran sulfate did not augment the production of GM-CSF in macrophages. Therefore, GM-CSF spontaneously present in macrophages might be a prerequisite for the induction of DNA synthesis.

Animals↗
PubMed1998

Structure-activity relationships of lipopolysaccharide (LPS) in tumor necrosis factor-alpha (TNF-alpha) production and induction of macrophage cell death in the presence of cycloheximide (CHX) in a murine macrophage-like cell line, J774.1.

The structure-activity relationships of lipopolysaccharide (LPS) in tumor necrosis factor-alpha (TNF-alpha) production and induction of macrophage cell death in the presence of cycloheximide (CHX) were examined in a murine macrophage-like cell line, J774.1. TNF-alpha production is one of the characteristic phenotypes of LPS-activated macrophages, and is observed upon incubation with LPS. On the contrary, macrophage cell death, which had been found in our laboratory (Amano F., Karahashi H., J. Endotoxin Res., 3, 415423 (1996)) and was examined as the release of lactate dehydrogenase (LDH) from cells into the culture supernatant, was observed 2.5 h after the addition of LPS in the presence of CHX. However, both TNF-alpha production and macrophage cell death were similarly dependent on the structures of LPS and lipid A. At more than 10 ng/ml, wild-type LPS from E.coli and S. minnesota exhibited the highest activity, and LPS as well as diphosphoryl lipid A from S. minnesota rough mutants also exhibited activity, but E. coli LPS detoxified by alkaline treatment or monophosphoryl lipid A from S. minnesota exhibited no activity even at 100 ng/ml. These results suggest that LPS-induced macrophage cell death in the presence of CHX shows similar requirements for LPS and/or lipid A structures as for the macrophage activation at higher doses than 10 ng/ml, although the former was not observed at 1 ng/ml LPS, while the latter was. However, TNF-alpha does not seem to be involved in the induction of macrophage cell death, because a neutralizing anti-TNF-alpha antibody failed to block the macrophage cell death and because recombinant TNF-alpha had little effect on the extent of LDH release in the presence or absence of LPS and/or CHX, and also because TNF-alpha production by LPS was abolished in the presence of CHX.

Animals↗
PubMed1986

Monoclonal antibodies reactive with chicken peritoneal macrophages: identification of macrophage heterogeneity.

Mouse monoclonal antibodies (MCAs) were prepared against chicken inflammatory macrophages for the purpose of analyzing macrophage heterogeneity. Macrophage-rich adherent peritoneal exudate cells harvested from Cornell K-strain chickens 42 hr after stimulation with Sephadex were used as immunogens in the production of the monoclonal antibodies. Eight hybridoma clones producing antibodies reactive with chicken peritoneal macrophages were subjected to characterization. While six of the monoclonal antibodies cross-reacted with various hematopoietic cell types, two MCAs (CMTD-1 and -2) were restricted in reactivity to macrophages. CMTD-1 was found to react with activated peritoneal macrophages generated by several irritants. In contrast, CMTD-2 identified a subpopulation of macrophages elicited by specific carbohydrate-based stimulants. This presumably was based on the cross-reaction of this MCA with specific carbohydrate linkages. Analysis using flow cytometry revealed the time-dependent appearance of CMTD-2-positive peritoneal macrophages between 24 and 52 hr after ip Sephadex injection. This subpopulation of peritoneal macrophages was found to be heterogeneous for the ability to undergo in vitro phagocytosis of sheep erythrocytes. CMTD-2-positive cells were also detected in the thyroids of 2-week-old Obese strain chickens with spontaneous autoimmune thyroiditis and at a low incidence in the spleens of normal chickens.

Animals↗
PubMed1989

Differential effect of recombinant granulocyte macrophage colony-stimulating factor on human monocytes and alveolar macrophages.

The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF), a pluripotent cytokine, on tumoricidal activity of alveolar macrophages and monocytes from nonsmoking normal volunteers was compared using [3H]thymidine-labeled human tumor cells (SK-MEL-28, melanoma) as targets. A dose-response study (500-5000 units/ml) of recombinant GM-CSF indicated dramatic differences between cytotoxicity of alveolar macrophages and blood monocytes. Macrophages exhibited significant (P less than 0.01) tumoricidal activity at all GM-CSF doses tested. In contrast, monocytes showed no significant tumoricidal activity at 500 units/ml and significantly (P less than 0.01) less activity than alveolar macrophages at doses of 1000-5000 units/ml. Maximal activity in alveolar macrophages occurred 72-96 h after exposure to 1000-5000 units/ml GM-CSF. Tumoricidal activity may be related to the state of maturation, because monocytes matured in vitro for 7 days displayed enhanced tumoricidal activity after GM-CSF exposure. Tumor necrosis factor alpha and interleukin 1 beta were measured in supernatant fluids of 24-h GM-CSF-treated cells. No significant increase in either cytokine was detected after GM-CSF treatment of alveolar macrophages. Monocyte interleukin 1 beta secretion was not enhanced by GM-CSF; however, tumor necrosis factor alpha secretion was enhanced in some donors (three of five). Superoxide anion production of alveolar macrophages was not enhanced by GM-CSF. These data suggest that alveolar macrophage tumoricidal activity is induced by GM-CSF and is not dependent on oxidative metabolism or secreted forms of interleukin 1 beta or tumor necrosis factor alpha.

Adult↗
PubMed1988

Granulocyte/macrophage colony-stimulating factor stimulates monocyte and tissue macrophage proliferation and enhances their responsiveness to macrophage colony-stimulating factor.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a specific humoral growth factor that stimulates both neutrophilic granulocyte and macrophage production by bone marrow hematopoietic progenitor cells. GM-CSF also stimulates the proliferation and clonal growth of both tissue macrophages and blood monocytes. Although at low concentrations GM-CSF was unable to support the long-term growth of tissue macrophages, it greatly enhanced their responsiveness to macrophage CSF (M-CSF, or CSF-1). This effect was also observed by treating macrophages with GM-CSF for a short time. GM-CSF did not compete with M-CSF for binding to M-CSF receptors nor was it inactivated by treatment with anti-M-CSF antiserum. Treatment of tissue macrophages with GM-CSF led to a rapid but transient downregulation of M-CSF receptors; prolonged incubation at 37 degrees C, however, resulted in a restoration and upregulation of M-CSF receptors. Identical effects were observed with both native or recombinant GM-CSF. This study suggests that GM-CSF regulates tissue macrophage production by two modes of action: (a) direct stimulation of macrophage proliferation, and (b) enhancement of their responsiveness to M-CSF.

Animals↗
PubMed1988

Antibody-mediated erythrolysis and erythrophagocytosis by human monocytes, macrophages and activated macrophages. Evidence for distinction between involvement of high-affinity and low-affinity receptors for IgG by using different erythroid target cells.

Antibody-dependent cellular cytotoxicity (ADCC) and Fc receptor-mediated phagocytosis were determined with human monocytes, monocyte-derived macrophages and activated macrophages, using rabbit IgG-covered sheep red blood cells (EAs) and anti-D-treated human erythrocytes (EAhu) as target cells. Monocyte and macrophage-mediated ADCC were distinguished by different kinetics, monocytes lysing either target more rapidly than macrophages. Macrophage activation by recombinant IFN-gamma (rIFN-gamma) led to a marked increase in ADCC activity against EAhu. This manifested in increased lysis of optimally sensitized target cells, in a sustained lysis of target cells carrying low antibody densities, and as an enhanced resistance to lysis inhibition by competing fluid-phase inhibition by competing fluid-phase IgG. All these effects were less striking when EAs were the target cells. Phagocytosis of EAs by rIFN-gamma-treated cells was strongly suppressed, regardless of the amount of antibody on the target cells, and susceptibility to inhibition by fluid-phase IgG was slightly increased. By comparison, phagocytosis of EAhu was depressed to a lesser degree, and susceptibility to inhibition by fluid-phase IgG was reduced when macrophages were rIFN-gamma treated. These and other experiments suggested that the functional triggering of monocytes and macrophages by EAs involved, at least in part, low-affinity Fc receptors (FcR), whereas EAhu interacted with macrophages via high-affinity FcR. It is shown elsewhere that rIFN-gamma treatment of macrophages increases the expression of high-affinity FcR, but not low-affinity FcR (Jungi, Lerch & Brcic, 1987). Differences in the rIFN-gamma-induced functional alterations assessed with EAhu or with EAs are interpreted therefore as being a consequence of differential involvement of high-affinity FcR and of low-affinity FcR in mediating an effector function. For monitoring rIFN-gamma-induced alterations in the effector capacity EAs are more appropriate targets since up-regulation of high-affinity FcR has a smaller influence on the response to this type of target. Using metabolic inhibitors, ADCC could be dissociated from ingestion suggesting that ADCC is not a post-phagocytic event.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1988

Granulocyte-macrophage colony-stimulating factor enhances selective effector functions of tissue-derived macrophages.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is produced by a variety of cells at sites of exposure to antigens. GM-CSF has a stimulatory effect on a number of neutrophil functions, but the effect on macrophage function is less clear. We investigated the effect of purified murine recombinant GM-CSF on murine peritoneal macrophage oxidative metabolism, Fc-dependent phagocytosis, anti-Toxoplasma activity, and expression of class II major histocompatibility antigen (Iad). GM-CSF significantly increased phorbol myristate acetate- and zymosan-elicited H2O2 release by resident and thioglycollate-elicited macrophages after 48 hours in vitro. The effect of recombinant GM-CSF was blocked by polyclonal anti-GM-CSF antibody and was not altered by lipopolysaccharide (0.01 to 1.0 microgram/mL). GM-CSF also stimulated Fc-dependent phagocytosis by peritoneal macrophages, although the stimulation of resident macrophages (1.4-fold) was less dramatic than that of thioglycollate-elicited cells (2.1-fold). GM-CSF (at doses up to 100 U/mL) had no effect on macrophage anti-Toxoplasma activity or on expression of Iad. In addition to stimulating macrophage growth, GM-CSF selectively promotes the functional capacity of tissue-derived macrophages.

Animals↗
PubMed1987

Evidence for effects of interleukin 4 (B cell stimulatory factor 1) on macrophages: enhancement of antigen presenting ability of bone marrow-derived macrophages.

We have studied the effects of recombinant mouse interleukin 4 (IL 4) (previously known as B cell stimulatory factor 1) on the antigen-presenting ability of murine splenic B cells and bone marrow macrophages. Our assay is based on the induction of antigen-presenting ability in these cells after incubation with IL 4 for 24 hr. The presenting cells were then used to stimulate IL 2 production by antigen-specific, I-Ad-restricted T cell hybridomas, a response mainly dependent on the induction of Ia antigens. Consistent with our previously published data using partially purified natural IL 4, we show here that recombinant IL 4 (but not interferon-gamma (IFN-gamma) or IL 1) induces antigen-presenting ability in B cells. Recombinant IL 4 was also found to induce antigen-presenting ability in a cloned, bone marrow derived-macrophage cell line (14M1.4), and in normal bone marrow-derived macrophages. These macrophage populations also respond to IFN-gamma showing enhanced antigen-presenting ability (mediated by increased Ia antigen expression). A small but significant increase in Ia antigen expression was also detected in 14M1.4 macrophages induced with IL 4. However, additional analysis suggested that the effect of IL 4 on 14M1.4 is different from that of IFN-gamma, because IL 4 (but not IFN-gamma) is able to maintain the viability and increase the size of and metabolic activity of bone marrow macrophages. However, IL 4 may not affect all macrophages because the macrophage cell line P388D1, which responds to IFN-gamma, failed to show enhanced antigen-presenting function after stimulation with IL 4. These observations indicate that IL 4, a lymphokine previously considered to be B cell lineage specific, has effects on macrophages and may be involved in their activation.

Animals↗
PubMed1983

Tumor-associated macrophages of mouse mammary tumors. I. Differential cytotoxicity of macrophages from metastatic and nonmetastatic tumors.

Macrophages were isolated from a series of transplanted mouse mammary tumors, originally derived from a single spontaneously arising tumor, to determine whether macrophage content or function correlated with any of a wide range of tumor properties. None of the tumor cell lines differed significantly in susceptibility to killing by MVE-2-activated peritoneal macrophages (cytotoxicity ranged from 40 to 63%). No significant differences were observed in macrophage content among the five tumor lines, nor was there any correlation between macrophage content and tumor weight, time since transplantation, or ability to metastasize. A significant association was observed, however, between a tumor's ability to metastasize to lung spontaneously and the tumoricidal activity of that tumor's infiltrating macrophages. Significant tumoricidal activity was seen when macrophages isolated from every metastatic tumor studied were used, whereas macrophage-mediated tumoricidal activity was observed in only 35% (6 of 17) of nonmetastatic tumors. Macrophage cytotoxicity was associated with spontaneous metastasis and not with lung colony formation per se.

Animals↗