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At least 973 records · Page 54Linked to original sources
PubMed1993

Failure to obtain hybridomas between human macrophages and human tumoral U-937 cells is probably due to parental macrophages.

Despite more than 50 attempts and the use of various methods, it has been impossible to establish homologous hybridomas between human mature macrophages and 8-azaguanine-resistant U-937 clones prepared in the laboratory. To rule out the possibility that these clones were unsuitable for the selection of hybrids, a study of their properties was done. It was shown that U-937 wild type cells were able to produce HPRT, whereas 8-azaguanine (8-aza)-resistant clones did not. Curiously, exonic and intronic HPRT sequences were undetectable both in wild type and in 8-aza-resistant cell genomes, under conditions where they were detected in control cells. Chromosome analysis of the clone UM9, one of the most frequently used in fusion experiments, revealed many qualitative and quantitative differences with the U-937 wild type cells. 8-aza-resistant U-937 cells were capable of fusion with human macrophages and gave rise to heterokaryons and probably to synkaryons, which survived for weeks without dividing in hypoxanthine-aminopterin-thymidine medium. The results could be interpreted in terms of the existence of a transacting negative regulatory mechanism of the macrophage genome on the proliferative capacity of homospecific hybridomas.

Animals↗
PubMed1986

In vitro interactions of murine peritoneal macrophages and sarcoma cells. I. Promotion of tumor cells proliferation by macrophages.

An ascites subline (AA) of the murine sarcoma MC1M grows in vivo in the peritoneal cavity but dies in vitro when cultured on glass or collagen. The viability of AA cells in vitro is not influenced in cocultures with fibroblast cell line L929, and is diminished in cocultures supplemented with macrophage culture supernatant or in cocultures with non-adherent peritoneal cells. However, AA cells proliferate in vitro on glass or collagen when cocultured with syngeneic, semisyngeneic, and allogeneic peritoneal macrophages. This was demonstrated by tritiated thymidine incorporation assay, by AA cell number counting, and by measuring AA cell protein content. Proliferation also occurs when AA cells are separated from the macrophage monolayer by millipore filters.

Animals↗
PubMed1983

The interaction of carbamylated low-density lipoprotein with cultured cells. Studies with human fibroblasts, rat peritoneal macrophages and human monocyte-derived macrophages.

We determined the effects of various degrees of chemical modification of low-density lipoprotein (LDL) on its interaction with receptors present on human fibroblasts, human monocyte-derived macrophages and rat peritoneal macrophages. We isolated LDL (d = 1.019-1.063 g/ml) and carbamylated different numbers of lysine residues and tested its cell-interactive properties, including binding, degradation, and stimulation of [3H]oleate incorporation into cholesteryl oleate. Small carbamylation of LDL (approximately 1-2% of lysine residues) resulted in a reduced ability (70-80% of control) to displace 125I-labeled LDL from fibroblast receptors. Modification of 12.5-25% of lysine residues resulted in a marked increase in the ability of LDL to interact with scavenger receptors and an almost total loss in the ability to interact with apolipoprotein B-E receptors. Acetylated LDL and malondialdehyde-modified LDL inhibited competitively the degradation of 125I-carbamylated LDL by human macrophages. Thus, the extent of modification plays an important role in recognition of modified LDL by scavenger receptors. There also seems to be a range of modification over which LDL is not yet recognized by the scavenger receptor, but its interaction with the apolipoprotein B-E receptor is markedly reduced. This perhaps explains how a small in vivo modification of LDL can result in an increase in residence time of LDL in the subendothelial tissue which can lead to further local interactions, ultimately increasing the atherogenicity of the LDL particle.

Animals↗
PubMed1990

Induction of nuclear lamins A/C in macrophages in in vitro cultures of rat bone marrow precursor cells and human blood monocytes, and in macrophages elicited in vivo by thioglycollate stimulation.

Hemopoietic cells from blood and bone marrow of mammals usually do not express lamins A/C but only lamin B, and this feature distinguishes these cells from the vast majority of somatic cells of the adult animal, which reveal lamins A/C as well as lamin B. Here we have cultivated rat bone marrow precursor cells and human monocytes isolated from peripheral blood in tissue culture supplemented with certain growth factors. These conditions allow bone marrow precursor cells and monocytes to differentiate almost quantitatively into accessory cells and/or mature macrophages. The different cell types in the cultures can be identified both morphologically and by other assays. Antibodies specific for mouse A/C lamins, human A/C lamins, or B lamins have been used to define the lamin complement as a function of time in culture and of cell type. A dramatic increase in lamin A/C-positive cells was observed in the first 3 days of culture with both accessory cells and macrophages expressing lamins A/C as soon as such cell types could be identified. Parallel in vivo experiments showed that treatment with thioglycollate caused the percentage of lamin A/C-positive peritoneal macrophages to increase from 5 to 80% between Days 0 and 6.

Animals↗
PubMed1990

Macrophage proteases can modify low density lipoproteins to increase their uptake by macrophages.

When low density lipoprotein (LDL) was incubated with sonicated macrophages at acidic pH, its protein moiety was partially degraded by cathepsins B and D. The reisolated LDL was taken up by intact macrophages up to about 20 times as fast as control LDL. LDL proteolysis and its enhanced uptake could be inhibited almost entirely by the selective protease inhibitors leupeptin and pepstatin. If macrophages in atherosclerotic lesions were to release acidic proteases (either by exocytosis or following cell death) and these were to modify LDL, this may help to explain why so much cholesteryl ester accumulates in these cells.

Animals↗
PubMed1986

Potential role of activated macrophages in acetaminophen hepatotoxicity. II. Mechanism of macrophage accumulation and activation.

Treatment of rats with acetaminophen (1.2 g/kg) results in the accumulation of activated macrophages in the centrilobular regions of the liver. To study the mechanism by which these cells accumulate and become activated, we examined the release of chemotactic and activating factors from cultured hepatocytes treated with acetaminophen (10-100 microM). We found a dose- and time-related generation of Kupffer cell and monocyte chemotactic activity by acetaminophen-treated hepatocytes. The maximum response was observed with a 25% dilution of medium collected 24 hr following treatment of hepatocytes with acetaminophen. Using a checkerboard assay, the factor in conditioned medium was determined to induce chemotaxis as well as chemokinesis in both Kupffer cells and monocytes. The hepatocyte-derived chemotactic factor was also found to be stable to freeze-thawing but to lose activity following heat or trypsin treatment. These results, together with our findings that chemotactic activity was eluted in the void volume following Sephadex G-25 size exclusion chromatography, suggested that the chemotactic factor released by hepatocytes is a large molecular weight protein. The release of Kupffer cell activating factors by acetaminophen-treated hepatocytes was also examined. Hepatocyte-conditioned medium was found to stimulate Kupffer cell phagocytosis and superoxide anion release, two characteristics of activated macrophages. These effects were maximal with conditioned medium collected from hepatocytes 24 hr following treatment with 50-100 microM acetaminophen. Acetaminophen alone had no effect on chemotaxis, phagocytosis, or superoxide anion production by Kupffer cells or monocytes. Taken together, these results suggest that macrophage accumulation and activation in the liver following acetaminophen treatment may be mediated, at least in part, by factors released from hepatocytes.

Acetaminophen↗
PubMed1991

Subarachnoidal macrophages share a common epitope with resident non-cerebral macrophages and show receptor-mediated endocytosis of albumin-gold and IgG-gold complexes.

Cerebral macrophages are supposed to exploit a pivotal role in scavenger functions of the central nervous system. We have examined the in vivo uptake of serum albumin and IgG conjugated with colloidal gold by subarachnoidal macrophages. These serum-borne proteins are endocytosed by receptor-mediated endocytosis by varying kinetics. Albumin-gold conjugates were found to be associated to a significant amount with coated pits and coated vesicles 1 min after superfusion of the cerebral surface. Within 25 min the major fraction of albumin-gold was transferred to the lysosomal compartment. IgG-conjugates revealed a less pronounced uptake. The uptake of albumin-gold could be competed by saturating of the 'receptor sites' with free albumin. It is suggested that the described receptor-mediated uptake of serum-borne proteins by subarachnoidal macrophages serves a cleansing function following blood-brain barrier disruption during acute or subacute inflammatory reactions.

Animals↗
PubMed2006

Macrophage MHC receptor 2: a novel receptor on allograft (H-2D(d)K(d))-induced macrophage (H-2D(b)K(b)) recognizing an MHC class I molecule, H-2K(d), in mice.

We previously reported that a population of allograft (H-2D(d)K(d))-induced macrophages (AIM) in C57BL/6 (H-2D(b)K(b)) mice exhibited major histocompatibility complex (MHC) haplotype (H-2D(d)) specific killing of the allograft (e.g., BALB/c skin and Meth A cells; H-2D(d)K(d)) in a macrophage MHC receptor (MMR)-dependent manner. In the present study, we isolated a cDNA clone encoding a novel receptor (MMR2) on AIM recognizing another MHC class I molecule, H-2K(d), by the expression cloning method using H-2K(d) tetramer and a monoclonal antibody (mAb; R12) specific for AIM. The cDNA (2359-bp) encoded a 677-amino acid polypeptide of a calculated molecular mass of 87 kDa and was found to be expressed exclusively on AIM among cells infiltrating into allografts on days 0-9 after transplantation. Confocal microscopy showed that HEK293T cells transfected with this cDNA were reactive toward the H-2K(d) molecule but not toward other MHC class I molecules such as H-2D(d), H-2D(b), H-2D(k), H-2K(b), H-2K(k), and H-2L(d) molecules. The binding of the H-2K(d) molecule to the transfectants was inhibited by the addition of R12 or anti-H-2K(d), but not by R15 (a mAb specific for H-2D(d) receptor) or anti-H-2D(d), mAb. Flow cytometric analysis revealed specific binding of H-2K(d) molecules to AIM (K(d)=2.7x10(-9) M); and the binding was completely suppressed by the addition of R12 mAb. These results demonstrate that a novel receptor (MMR2) for H-2K(d) molecules was induced on effector macrophages responsible for allograft (H-2D(d)K(d)) rejection by H-2D(b)K(b) mice.

Amino Acid Sequence↗
PubMed2002

Role of estrogen in the regulation of cholesteryl ester synthesis in macrophages: the interaction between native and modified low density lipoprotein and human monocyte-derived macrophages.

OBJECTIVES: To study the effects of estrogen on the changes in cholesterol esterification induced by native and modified low density lipoprotein (LDL) in macrophages. DESIGN AND METHODS: Human monocyte-derived macrophages (HMDM) were used, and the influence of the presence of 17beta estradiol in the short term, and during the maturation of the cells, on the esterification of cholesterol from native (nLDL), acetylated (acLDL) and oxidized (oxLDL) LDL was determined. RESULTS: In the short-term (6 h), 17beta estradiol (1.5 x 10(-6)M) did not affect the esterification of cholesterol from acLDL or oxLDL, but with native LDL (nLDL) a 1.5-fold increase was observed. In contrast, long-term exposure of HMDM during maturation to 17beta-estradiol (1.5 x 10(-9)M - 1.5 x 10(-5)M) decreased cholesterol esterification in the presence of oxLDL and acLDL, but not nLDL. CONCLUSIONS: These results suggest that both the time of exposure and the concentration of estrogen used influence its effects on the interaction between HMDM and LDL, and thus on macrophage foam cell formation.

Cell Differentiation↗
PubMed1978

Killing of untreated target cells by nonimmunized rat macrophages in vitro. II. Ultrastructural studies on the interaction of macrophages and rat liver cells.

The sequence of morphological changes following the interactions between macrophages of nonimmunized rats and allogeneic liver cells in vitro were examined by scanning and transmission electron microscopy. The effector cells could be identified as macrophages because of their morphologic characteristics and their ability of latex beads incorporation. The cytotoxic reactions required close contracts between the reactive cells. Effector membrane processes and microvilli attached the target cell surface. Broad contacts and, more frequent, point contacts were observed. After 4 to 5 hrs of incubation the target cells showed pinocytotic activities in the contact regions. Later on submembraneous cytoplasmatic leaks or defects indicated the increasing damage of the target cells. Finally, liver cell ghosts with degenerated organelles were found as morphologic expression of general target cell destruction whereas effector macrophages did not show any damage during the cytotoxic reaction.

Animals↗
PubMed2002

Targeting to macrophages: role of physicochemical properties of particulate carriers--liposomes and microspheres--on the phagocytosis by macrophages.

Heterogeneous functions of macrophages in human immune systems have renewed interest in targeting of drugs to these cells. Various carrier systems have emerged to deliver drugs to macrophages, albeit the efficacy, reliability and selectivity of these carriers are still in question. To date, the most extensively studied carriers are liposomes and microspheres. Various physicochemical properties of these carriers can alter their efficacy and specificity to a great extent. These properties include hydrophilicity, surface charge, composition, concentration, and presence of various ligands. In this review, a comprehensive evaluation of the literature has been carried out in order to show the role of these parameters in the design of carriers for targeting of drugs to macrophages.

Animals↗
PubMed1984

Extracellular cytolysis by activated macrophages: studies with macrophages on permeable membranes.

Mouse peritoneal macrophages were allowed to adhere to discs cut from permeable membranes, then activated by incubation in lymphokine-rich supernates from ConA-stimulated spleen cells. Such filter-borne cultures of activated macrophages (AM) were cytotoxic for various target cells (Tc). The kinetics of the cytotoxic process could be monitored by removal of the filter-bound AM after increasing times of contact with Tc. Using 3 assay procedures to assess macrophage cytotoxicity, i.e. chromium-51 release, thymidine incorporation, and cloning inhibition, most of the damage to Tc was found to occur within 30 min to 2 h of interaction between the two cell types. The kinetics of the cytolytic effect were similar, whether Tc were in direct contact with AM or separated by the filter; thus cytotoxicity appeared to be mediated by a highly diffusible compound. Supernates of AM incubated with Tc for 1 to 4 h, but not of AM incubated alone, were toxic for Tc, suggesting that Tc provide a signal to AM, in the absence of which toxic intermediates fail to be released. Addition of catalase or peroxidase considerably reduced Tc destruction by AM, indicating that oxygen metabolites might play a role as mediators of AM cytotoxicity in the present experimental model.

Animals↗
PubMed1984

Macrophages as regulatory cells in mitogen induced spleen cell proliferation. 1. Macrophages as suppressor cells.

In this study the effect of alveolar (AC) or peritoneal (PC) lavage cells from Lewis rats on the mitogen induced proliferation of syngeneic spleen cells was investigated. When total spleen cells were stimulated with PHA (5 micrograms/ml) or ConA (6 micrograms/ml), the addition of AC or PC and of their adherent (A) or non-adherent (NA) fractions had dose dependent suppressive effects. After passing the spleen cells through a Sephadex G-10 column, the eluted cells responded poorly to the mitogens. Addition of low numbers (2 X 10(3) = 1%) AC or NA-AC improved this response, whereas higher concentrations (5 or 10%) of these cells or any concentration of A-AC, PC, A-PC or NA-PC showed either none or a suppressive effect. The cells which strongly suppress mitogen induced lymphocyte proliferation have macrophage morphology, are adherent, esterase positive, bear Fc receptor for IgG and bind ganglioside coated erythrocytes. NA-AC were further separated into Ia-depleted (Ia-) and Ia-enriched (Ia+) population. The Ia+ fraction contained 80 to 90% Ia bearing cells, supported the mitogen induced stimulation of Sephadex G-10 depleted spleen cells and was ineffective in suppression. Interestingly, these cells did not bind ganglioside treated sheep erythrocytes. On the other hand, the Ia-negative NA-AC fraction and particularly the A-AC population strongly expressed the "ganglioside receptor" as well as typical macrophage markers like Fc receptors, latex-phagocytosis and non-specific esterase. Therefore, the "ganglioside receptor" may be a useful marker to define suppressor macrophages.

Animals↗
PubMed1994

Modulation of intracellular formation of reactive oxygen intermediates in peritoneal macrophages and microglia/brain macrophages by propentofylline.

Ischemia-induced nerve cell death can partly be prevented by propentofylline, a pharmacon structurally related to xanthine derivates that interacts with the neuromodulatory function of endogenous adenosine. To evaluate a possible mechanism of neuroprotection by propentofylline, we studied its effect on the cellular production of reactive oxygen intermediates in microglial cells, which under pathological conditions can differentiate into brain macrophages, in comparison to peritoneal macrophages. Using a flow cytometric assay, we determined the intracellular formation of reactive oxygen intermediates by measuring the oxidation of the membrane-permeable and nonfluorescent dihydrorhodamine 123 to the cationic and intracellularly trapped, green fluorescent rhodamine 123 in single viable cells. Propentofylline at the therapeutic concentration of 50 microM completely inhibited the Ca(2+)-dependent Con A-induced increase in the production of reactive oxygen intermediates in peritoneal macrophages. In isolated and cultured microglial cells, which have a high spontaneous respiratory burst activity, the spontaneous production of reactive oxygen intermediates was reduced by approximately 30%. A phorbol 12-myristate 13-acetate-induced rise in the respiratory burst activity could not be inhibited by propentofylline in either cell type. An increased generation of reactive oxygen intermediates is thought to contribute to nerve cell death after brain ischemia, edema, and neurodegenerative diseases like Alzheimer's disease. These pathological conditions are all accompanied by an activation of microglial cells. We therefore suggest that the neuroprotective properties of propentofylline might in part be due to a modulation of the microglial production of potentially harmful reactive oxygen intermediates.

Animals↗
PubMed1997

myo-Inositol is an osmolyte in rat liver macrophages (Kupffer cells) but not in RAW 264.7 mouse macrophages.

The role of myo-inositol as an osmolyte was studied in cultured rat liver macrophages (Kupffer cells). Hyperosmotic exposure of Kupffer cells stimulated myo-inositol uptake and led to an increase in the mRNA levels for the sodium/myo-inositol cotransporter (SMIT). Conversely, hypo-osmotic (205 m-osM) exposure diminished myo-inositol uptake when compared with normo-osmotic (305 m-osM) control incubations. The hyperosmolarity-induced SMIT mRNA increase was counteracted by added myo-inositol or betaine. In contrast with Kupffer cells, there was only a slight hyperosmotic stimulation of myo-inositol uptake in RAW 264.7 mouse macrophages, and the myo-inositol transporter (SMIT) mRNA was not detectable. Further, a slight stimulation of taurine uptake and an increase in taurine transporter (TAUT) mRNA level by hyperosmolarity was observed in RAW 264.7 cells, whereas hypo-osmolarity led to a decrease in taurine uptake and TAUT mRNA level. When Kupffer cells were preloaded with myo-inositol, hypo-osmotic exposure led to a rapid efflux of myo-inositol from the cells. Myo-inositol efflux was also stimulated by phagocytosis of latex particles; however, latex was without effect on the hyperosmolarity-induced increase of SMIT mRNA levels. The results suggest a role of myo-inositol as an osmolyte in rat Kupffer cells but not in RAW 264.7 mouse macrophages. The functional relevance of this osmolyte strategy might lie in the maintenance of cell volume homeostasis during phagocytosis in Kupffer cells; however, the interplay with the other osmolytes betaine and taurine remains to be established.

Animals↗
PubMed2000

Selective inhibition of HIV replication in primary macrophages but not T lymphocytes by macrophage-derived chemokine.

Macrophage-derived chemokine (MDC) has been reported to inhibit different HIV-1 strains in activated peripheral blood mononuclear cells (T cell blasts), although other investigators have not confirmed these findings. Here we demonstrate that MDC inhibits the replication of CCR5-dependent (R5) HIV-1(BaL) in monocyte-derived macrophages (MDM), but not in T cell blasts, although with variable potency depending on donor variability. Analysis of HIV-1(BaL) proviral DNA synthesis in MDM indicated that the suppressive effect of MDC did not involve inhibition of early events such as entry or reverse transcription. Finally, an inverse correlation was observed between the levels of endogenous MDC secreted by uninfected MDM of different donors and the efficiency of different HIV strains, including two primary isolates with different coreceptor usage, to replicate in these cells. Thus, MDC represents an example of a chemokine inhibiting HIV replication in macrophages acting at one or more postentry levels in the virus life cycle.

Antiviral Agents↗
PubMed2001

alpha 1-Antichymotrypsin is the human plasma inhibitor of macrophage ectoenzymes that cleave pro-macrophage stimulating protein.

Macrophage stimulating protein (MSP) is secreted as 78-kDa single chain pro-MSP, which is converted to biologically active, disulfide-linked alphabeta chain MSP by cleavage at Arg(483)-Val(484). Murine resident peritoneal macrophages have two cell surface proteolytic activities that cleave pro-MSP. One is a pro-MSP convertase, which cleaves pro-MSP to active MSP; the other degrades pro-MSP. The degrading protease is inhibited by soybean trypsin inhibitor or by low concentrations of blood plasma, which allows the convertase to cleave pro-MSP to MSP. Using pro-MSP cleavage as the assay, we purified the inhibitor from human plasma. The bulk of the plasma protein was removed by salting out and by isoelectric precipitation of albumin. Highly purified inhibitor was then obtained in three steps: dye-ligand binding and elution, ion exchange chromatography, and high performance liquid chromatography gel filtration. After SDS-polyacrylamide gel electrophoresis and transfer to a polyvinylidene membrane, N-terminal sequencing of the product identified it as alpha(1)-antichymotrypsin. The mean concentration of alpha(1)-antichymotrypsin in human plasma is 7 micrometer. At this concentration, alpha(1)-antichymotrypsin inhibits both macrophage enzymes. A concentration of 0.4 micrometer, which is in the expected concentration range in extracellular fluid, preferentially inhibits the degrading enzyme, which allows for cleavage to active MSP by the pro-MSP convertase.

Animals↗
PubMed1976

Factors regulating macrophage production and growth: identity of colony-stimulating factor and macrophage growth factor.

The activities of a colony-stimulating factor (CSF), which stimulates granulocyte-macrophage colony formation by mouse hemopoietic cells, and macrophage growth factor (MGF), which stimulates proliferation of activated peritoneal macrophages, have been demonstrated by various criteria to reside in the same molecular species. These criteria include occurrence in various sources and copurification of the activities in mouse L-cell-conditioned medium as well as the biological, physicochemical, and antigenic properties of the activities of L-cell-conditioned medium. CSF and MGF activities of L-cell-conditioned medium are ascribable to a glycoprotein of mol wt approximately 60,000 which migrates electrophoretically with alpha-globulin. Human urinary CSF, which also possesses MGF activity, has similar properties and can be neutralized by antiserum to highly purified L-cell medium CSF. A procedure is described for the partial purification of material from L-cell medium that has activity at 1 ng/ml in both MGF and CSF assays.

Animals↗