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At least 811 records · Page 45Linked to original sources
PubMed1991

Recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) induces human macrophage production of transforming growth factor-alpha.

Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) is known as an inducer of proliferation and functional activation of myeloid cells. This study was carried out to characterize the effect of purified recombinant human GM-CSF (rhGM-CSF) on induction of TGF-alpha in macrophages. Using Northern blot analysis and immunoassays, we show here that rhGM-CSF markedly stimulates production of TGF-alpha messenger RNA and protein in normal tonsil macrophages. The findings are consistent with macrophages being a normal inducible source of TGF-alpha which may be an important mediator of various activities of GM-CSF both in hematopoietic and non-hematopoietic cells.

Animals↗
PubMed1991

The presence of sialidase-sensitive sialosylgangliotetraosyl ceramide (GM1b) in stimulated murine macrophages. Deficiency of GM1b in Escherichia coli-activated macrophages from the C3H/HeJ mouse.

The stimulated murine macrophage was found to contain 11 major gangliosides of which 8 were determined to be monosialylated. The thin-layer chromatographic patterns were complicated by the presence of both sialic acid and ceramide fatty acid heterogeneity. N-glycolyl and N-acetylneuraminic acid-containing species were present for each ganglioside characterized. Although C18 sphingosine was the only long chain base detected, ceramide fatty acid ranged from C16 to C24 carbon moieties. Based on gas-liquid chromatographic and antibody analyses, all major tetraosyl structure gangliosides were ganglio series types. Comprising 43 to 60% of thioglycollate-stimulated cells and 60 to 70% of Escherichia coli-activated cells, monosialosyl-gangliotetraosyl ceromides (Gm1 gangliosides) were the major monosialo species of which four were present: sialidase-resistant NeuGc-GM1a and NeuAc-GM1a and sialidase sensitive NeuGc-GM1b and NeuAc-GM1b. Analyses of thioglycollate-elicited murine peritoneal macrophage ganglioside patterns from four strains of mice, including the C3H/HeJ strain, indicated that, in the absence of any expression of a genetic defect, the pattern is conserved. However, when E. coli was used as the activating agent, the normal C3H/HeN macrophage contained little Gm1a with the sialidase-sensitive Gm1b predominant; the converse was true for the congenic endotoxin hyporesponsive C3H/HeJ strain. Therefore, C3H/HeJ mice are not defective in ganglioside metabolism per se but in the processing of an endotoxin stimulus such that one manifestation is an altered macrophage ganglioside pattern deficient in Gm1b.

Animals↗
PubMed1990

Human macrophage colony-stimulating factor induces macrophage colonies after L-phenylalanine methylester treatment of human marrow.

Macrophage-colony stimulating factor (M-CSF) has well-known effects on murine bone marrow, but its colony stimulating activity for human bone marrow is controversial. After treatment of human bone marrow with L-phenylalanine methylester (PME), macrophage-colonies (CFU-M) were induced by M-CSF in a dose-dependent fashion. The optimal concentration of recombinant human-macrophage colony stimulating factor (rhM-CSF) was 1,000 U/mL. Purified human urine M-CSF had colony stimulating activity similar to rhM-CSF. Further studies were performed to determine the factors responsible for the enhanced CFU-M formation from PME treated marrow. Compared with nylon wool and carbonyl iron monocyte depletion methods, PME eliminated significantly more monocytes and myeloid cells. This observation suggested that these cells may release hematopoietic inhibitory factors for CFU-M. Low concentrations (1%) but not normal (10%) concentrations of blood monocytes were inhibitory (mean inhibition, 48%) to CFU-M. High concentrations of monocytes (50%) augmented CFU-M colonies. HL-60 conditioned media was used to simulate secretory products of early myeloid cells. HL-60 conditioned media (1%) inhibited CFU-M formation but not granulocyte macrophage or granulocyte colonies. We conclude that M-CSF has colony stimulating activity for human marrow that can be recognized after removal of inhibitory cells by PME treatment.

Bone Marrow↗
PubMed1990

Release of granulocyte-macrophage colony-stimulating activity from human alveolar macrophages and its support of human myeloid blast cell proliferation.

The ability of human alveolar macrophages to support colony formation of precursor blast cells of the myeloid lineage was investigated. Myeloid blast cells were collected from patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and from the livers of fetuses aborted in the second trimester of gestation. It was found that the alveolar macrophages (AM) produced sufficient amount of colony-stimulating activity which culminated in the fourth week of in vitro cultivation. Conditioned media from AM supported the growth of multipotential blast cell colonies (GEMM-CFU) in AML and MDS, while in fetal hemopoiesis macrophage colonies preponderated. Preincubation with human interferon-alpha (IFN-alpha) can abrogate the production of the granulocyte-macrophage colony stimulating factor (GM-CSF) by AM. Media conditioned by AM were not able to compensate for cell-to-cell contact in long-term cultures of AML blast cells but CSFs released from AM in vivo can contribute to aggravation of the disease.

Bone Marrow↗
PubMed1987

Interferon-alpha, -beta, and -gamma augment the levels of rRNA precursors in peritoneal macrophages but not in macrophage cell lines and fibroblasts.

We have studied the ribosomal RNA content in murine peritoneal macrophages activated to cytotoxicity with interferon-alpha (IFN-alpha), interferon-beta (IFN-beta), and interferon-gamma (IFN-gamma). Total RNA was purified from IFN-alpha, -beta, or -gamma activated macrophages, and Northern blot analysis was performed by using subcloned fragments specific for precursor rRNA (pre-rRNA) as probes. All types of interferon (alpha, beta, gamma) at the doses normalized for induction of cytotoxic activity caused accumulation of 45S, 41S, and 36S pre-rRNA. In contrast, the levels of 32S pre-RNA and 28S, 5.8S, and 18S mature rRNA were not affected by IFN treatment. Therefore, the accumulation of pre-rRNA in macrophages activated to cytotoxicity by IFN was not paralleled by changes in total content of mature rRNA. No accumulation of pre-rRNA upon IFN treatment was found in a murine fibroblast cell line (L929 cells) or in a macrophage cell line (GG2EE) immortalized from bone marrow of C3H/HeJ mice. Neither of those cell lines become cytotoxic in response to IFN. Overall, our data support the concept that IFN acts selectively on the mechanism controlling the levels of some pre-rRNA and that the mechanism of IFN action involves the post-transcriptional control of ribosomal gene expression.

Animals↗
PubMed1986

Interleukin 3 (IL 3) regulates the in vitro proliferation of both blood monocytes and peritoneal exudate macrophages: synergism between a macrophage lineage-specific colony-stimulating factor (CSF-1) and IL 3.

The effect of interleukin 3 (IL 3) on regulation of macrophage proliferation was examined. Although IL 3 alone stimulates the colony formation in bone marrow cells, it fails to stimulate the colony formation by both peritoneal exudate macrophages (PEM) and blood monocytes. However, IL 3 greatly enhances the proliferative capacity of both PEM and monocytes in responding to suboptimal concentrations of CSF-1. At supraoptimal concentrations of CSF-1, IL 3 did not increase the number of colonies, but greatly increased colony size. Kinetic studies showed that IL 3 enhances CSF-1-induced macrophage proliferation by shortening the cell doubling time. Monocytes were more sensitive to the action of IL 3 and possessed higher proliferative potential than PEM. Binding studies with radioactive labeled CSF-1 (125I-CSF-1) showed that IL 3 treatment induced an increased expression of CSF-1 receptor activity by PEM which appears to be a result of increased number of available receptor sites. The effect of IL 3 on the expression of receptor activity is both dose- and time-dependent. IL 3 also augments the rate of receptor-mediated CSF-1 endocytosis by PEM which appears to be a direct result of increased expression of CSF-1 binding sites. These results demonstrate that, in addition to stimulating the growth and differentiation of several blood cell lineages by hemopoietic stem cells, IL 3 also possesses the ability to modulate CSF-1 receptors, thereby affecting proliferation of more mature blood monocytes and tissue-derived macrophages.

Animals↗
PubMed1988

Response of resident murine peritoneal macrophages to in vivo administration of granulocyte-macrophage colony-stimulating factor.

The effect of s.c. inoculation of purified recombinant derived granulocyte-macrophage (GM)-CSF on resident murine peritoneal macrophages was assessed in this study. From 18 to 24 h after s.c. administration of GM-CSF to normal mice, the resident peritoneal macrophages were harvested and the levels of membrane-bound IL-1, FcR, Mac-1 cell-surface Ag, and class II MHC expression were assessed. Peritoneal cells from GM-CSF-inoculated mice had significantly greater levels of membrane-bound IL-1 than did control mice. In addition when resident peritoneal macrophages from normal mice were purified by adherence and grown in the presence of GM-CSF, they produced greater levels of both membrane-bound and secreted IL-1. The peritoneal cells from GM-CSF-inoculated mice did not differ from controls in the expression of class II MHC-encoded Ag. This observation was confirmed by the finding that GM-CSF was unable to induce class II MHC expression on P388D1 cells, whereas a secondary mixed leukocyte culture supernatant was. Peritoneal cells from GM-CSF-inoculated mice also exhibited greater levels of expression of FcR and the Mac-1 cell-surface Ag. This resulted in an increase in their ability to phagocytose opsonized SRBC in vitro.

Animals↗
PubMed1987

In vivo macrophage-directed lymphocyte traffic requires macrophage activation.

Lymphocytes are attracted to activated macrophages in tissue. In the absence of exogenous activators, only syngeneic macrophages can become sufficiently activated, to produce lymphocyte attractants. Allogeneic macrophages require exogenous activation to accomplish lymphocyte recruitment. It is likely that graft rejection is initiated by a nonspecific inflammatory reaction within the graft. Once host macrophages have entered the graft they may be activated by the inflammatory process to produce lymphocyte attractants. As lymphocytes are called to the graft, those recognizing donor determinants may expand to effect graft loss.

Animals↗
PubMed1985

Immune complex effects on murine macrophages. II. Immune complex effects on activated macrophages cytotoxicity, membrane IL 1, and antigen presentation.

We investigated the effects of immune complexes on macrophage functions in vitro. Immune complexes inhibit lymphokine induction of both I-Ak expression and cytotoxic activity by fetal calf serum elicited macrophages during long-term (7 days) culture. In addition, induction of antigen presentation was significantly inhibited by immune complexes. Expression of membrane interleukin 1 (IL-1) (a membrane-bound bound form of the T cell mitogen required for antigen presentation by fixed cells) was minimally inhibited by immune complexes. Therefore, inhibition of antigen presentation was primarily due to effects on Ia expression rather than membrane IL 1 expression. The inhibitory effect of immune complexes was not found during short-term culture (4 to 48 hr) when activated macrophages (bearing high levels of Ia) from mice infected with Listeria monocytogenes were examined. Immune complexes maintained or even increased levels of both I-Ak and cytotoxicity in activated macrophages. The implications of these findings for immune complex modulation of the immune response are discussed.

Animals↗
PubMed1985

Priming and triggering of tumoricidal and schistosomulicidal macrophages by two sequential lymphokine signals: interferon-gamma and macrophage cytotoxicity inducing factor 2.

We describe a new lymphokine activity, macrophage cytotoxicity inducing factor 2 (MCIF2), in the T cell mitogen-induced supernatant of a murine T cell clone in long-term culture. MCIF2 has the following properties: it elutes from a Sephadex G-100 column in three m.w. forms (10, 34, and 100 KD); it is acid labile (pH 2 to 4) and heat sensitive (80 min at 56 degrees C); it is not constitutively secreted, coexists in the same supernatant with immune interferon (IFN-gamma), and synergizes with IFN-gamma for induction of tumoricidal and schistosomulicidal resident peritoneal mouse macrophages. We uncoupled this synergy and show that IFN-gamma serves as the first ("priming") and MCIF2 as the second ("triggering") signal for macrophage activation. Application of the lymphokines in the reverse order was ineffective. These data demonstrate a two-step mechanism of macrophage activation.

Animals↗
PubMed1983

Macrophage-activating factors from different T cell clones induce distinct macrophage functions.

The data reported in this paper are the first demonstration that different T cell clones (PC-AKR-CI 96, clone 96; PK 7.1.2 E8, clone 7.1.2 E8) secrete different macrophage-activating factors (MAF) that induce distinct macrophage activities. Incubation of resident murine macrophages with MAF 7.1.2 E8 increased RNA, protein, and glycoprotein synthesis, hexosemonophosphate shunt (HMPS) activity, release of oxygen metabolites (O-2, H2O2), pinocytosis, phagocytosis, and tumor cytostasis, whereas no effect on prostaglandin E (PGE) release, schistosomula killing, and tumor cytolysis could be observed. In contrast, MAF 96 increased glycoprotein synthesis, HMPS activity, release of oxygen metabolites and PGE, schistosomula killing, and tumor cytostasis and cytolysis, whereas RNA and protein synthesis and pinocytosis were decreased and phagocytosis remained unaffected. Thus, MAF from both T cell clones share some macrophage-activating properties but differ in others. Most importantly, both MAF could be differentiated serologically by a rabbit anti-lymphokine antiserum that selectively inhibited MAF 96 but not MAF 7.1.2 E8 activity. At optimal concentrations, MAF 96 and 7.1.2 E8 were active in the absence of lipopolysaccharide (LPS) whereas LPS enhanced the activity of suboptimal doses of MAF 96 but not of MAF 7.1.2 E8. These data are discussed with respect to the possibility that the functional dichotomy of T cell clones might reflect different activities of normal T cell subpopulations.

Animals↗
PubMed1984

Intracellular destruction of Leishmania tropica by macrophages activated with macrophage activating factor/interferon.

Supernatants (SN) from cloned T cell lines, lymphokine secreting tumour cell lines and mixed lymphocyte culture were analysed for their ability to induce murine peritoneal exudate cell (PEC) macrophages (M phi) parasitized with Leishmania tropica to destroy the parasite. The ability of the SN to induce parasite destruction in parasitized PEC M phi correlated with their content of macrophage activating factor/interferon. Neither granulocyte-macrophage colony stimulating factor, M phi colony stimulating factor nor interleukin 2 was required for the induction of parasiticidal activity by infected PEC M phi. Similar results were also obtained using either a different Leishmania species, Leishmania enriettii, or a second source of cells: bone marrow derived macrophages.

Animals↗
PubMed1983

Immunoregulation by macrophages II. Separation of mouse peritoneal macrophages having tumoricidal and bactericidal activities and those secreting PGE and interleukin I.

Macrophage subpopulations having bactericidal or tumoricidal activities and secreting interleukin I (IL1) or prostaglandin E (PGE) were identified through primary or secondary infection with Salmonella enteritidis and separated by sedimentation velocity. Bactericidal activity was measured by [3H]-thymidine release from Listeria monocytogenes and tumoricidal activity by 51Cr-release from C-4 fibrosarcoma or P815 mastocytoma cells. Macrophages with bactericidal activity were distinguished from those with tumoricidal activity a) during secondary infection when cytolytic activity occurred only at days 1-4 post injection and bactericidal activity remained high throughout and b) after sedimentation velocity separation. Cytolysis was consistently greatest among adherent cells of low sedimentation velocity, whereas cells with bactericidal activity increased in size during the infection. Tumour cytostasis (inhibition and promotion of [3H]-thymidine uptake) differed from cytolysis in that the former was more prolonged during infection and was also detected among large cells. Secretion of immunoregulatory molecules PGE and IL1 occurred maximally among different macrophage subpopulations separated by sedimentation velocity and depending on the type of stimulus used in vitro. There was an inverse correlation between IL1 production and PGE production after stimulation with C3-zymosan or lipopolysaccharide (LPS). The development of immunity during infection may therefore be dependent upon the relative proportions of effector and regulatory macrophage subpopulations and the selective effects of environmental stimuli on these functions.

Animals↗
PubMed1994

Macrophage-stimulating protein inhibits induction of nitric oxide production by endotoxin- or cytokine-stimulated mouse macrophages.

Human serum macrophage-stimulating protein (MSP) is a disulfide-linked heterodimer that induces motile and phagocytic activity of mouse resident peritoneal macrophages. In this work, we found that MSP blocked the increase in macrophage nitric oxide synthase mRNA, as well as the associated increase in nitric oxide production, that occurred in response to several stimuli. These included bacterial products and mammalian cytokines: endotoxin, and interferon-gamma plus endotoxin, interleukin-2, or tumor necrosis factor-alpha. The inhibition by MSP of induction of nitric oxide synthase mRNA and nitric oxide secretion was concentration-dependent. The concentration of MSP that caused maximal inhibition of nitric oxide production was comparable with the optimum for stimulation of macrophage motile and phagocytic activity. Time course studies showed that nitrite was first detected in culture fluid about 8 h after endotoxin stimulation, and it accumulated at a linear rate during the ensuing 16 h. Inhibition by MSP occurred during the 8-h lipopolysaccharide (LPS) induction period; inhibition was maximal when MSP and LPS were added together and decreased progressively to no inhibition as the interval between LPS and MSP addition increased to 11 h.

Amino Acid Oxidoreductases↗
PubMed1994

Effect of human recombinant granulocyte-macrophage colony-stimulating factor and IL-3 on the expression of surface markers of human monocyte-derived macrophages in long-term cultures.

Granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-3, which are involved in the maturation of cell precursors in the bone marrow into granulocytes and macrophages, were found also in chronic inflammatory sites, and their production might be enhanced by inflammatory stimulants. These findings led us to examine the effect of human recombinant GM-CSF (hrGM-CSF) and hrIL-3 on the maturation of human peripheral blood monocytes in long-term tissue cultures and on the expression of functional membrane bound molecules. Adherent human peripheral blood monocytes cultured for 2 weeks in the presence of GM-CSF or IL-3 were examined for viability and adherence, expression of membranal HLA-DR, CD-14, and IL-1 alpha, and LPS triggered TNF-alpha production. GM-CSF and IL-3 treatment increased the viability of adherent cells after 2 weeks in culture, and elevated the expression of membranal HLA-DR, CD-14 (LPS receptor), and IL-1 alpha. Such treated macrophage cultures also showed elevated production of TNF-alpha. The results indicate that GM-CSF and IL-3 facilitate the long-term maturation of monocytes into macrophages, augment their capacity to bind LPS, and elevate the release of cytokines involved in inflammatory and granulomatous reactions.

Antigens, CD↗
PubMed1976

Guinea pig lymphocyte-derived macrophage aggregation factor: its separation from macrophage migration inhibitory factor.

Lymphocytes from guinea pigs having delayed hypersensitivity to horse-radish peroxidase (HRPO) when cultured in vitro with HRPO produce a large m.w. factor (greater than 100,000 daltons) that causes peritoneal macrophages from nonimmune animals to aggregate. The macrophage aggregation factor (MAF) can be separated from macrophage migration inhibitory factor (MIF) by gel filtration of active lymphocyte supernatants on Sephadex G-150. MAF is heat stable (56 degrees C for 30 min) but inactivated by trypsin. These data suggest that aggregation of macrophages in vitro by lymphokine-rich culture supernatants is not due to MIF but is caused by a separate large m.w. factor.

Animals↗
PubMed1996

Regulation of murine macrophage IL-12 production. Activation of macrophages in vivo, restimulation in vitro, and modulation by other cytokines.

IL-12 is important in the host response to a variety of pathogens. It plays an adjuvant-like role in an initial immune response as well as a therapeutic role in established infections. Despite its well documented importance, comparatively little is known about the regulation of IL-12 production. In this study, we examined IL-12 production by cultured murine peritoneal macrophages from two perspectives: 1) macrophage activation in vivo, and 2) stimulation of IL-12 secretion in vitro. Macrophages were maximally activated within 48 h in vivo during infection with Listeria. Interestingly, although avirulent or heat-killed Listeria induced only minimal production of IL-12 by macrophages, the immunogenic combination of heat-killed bacteria and rIL-12 was highly stimulatory for IL-12 production. LPS and peritoneal inflammatory agents were also stimulatory, but latex beads were ineffective, indicating that microbial components were essential and phagocytosis alone was insufficient. Restimulation in vitro revealed similar patterns, in that infection and LPS were stimulatory but latex beads were not. A systematic survey of potential stimulatory agents showed that microbial heat shock proteins, crude bacterial extracts, bacterial superantigens, a yeast extract, and dsRNA induced IL-12 in vitro. Other cytokines also influenced IL-12 induction. IFN-gamma, which is up-regulated during infection, acted in synergy with other stimuli, suggesting an amplification loop for IL-12 production, whereas IL-4, IL-10, IL-13, and TGF-beta were inhibitory. The existence of a broad range of stimuli from a wide variety of pathogenic organisms underscores the fundamental importance of IL-12 in host defense.

Animals↗
PubMed1996

Dietary n-3 fatty acids increase spleen size and postendotoxin circulating TNF in mice; role of macrophages, macrophage precursors, and colony-stimulating factor-1.

In experimental studies in mice, dietary supplementation with n-3 fatty acids (FA) alleviates inflammation and increases resistance to infection. Nevertheless, TNF production capacity was found to be increased in n-3 FA-fed mice. We previously found increased relative spleen weights in n-3 FA-fed mice. In this study, the nature of this increased spleen size was further investigated. Spleen cellularity was increased significantly in mice fed n-3 FA (fish oil 15% w/w), compared with controls fed corn oil (15%) or normal lab chow (p < 0.05). Experiments with T cell-deficient nude mice and experiments using macrophage depletion through liposomal dichloromethylene-biphosphonate revealed that the increase in spleen cellularity is T cell independent and largely due to macrophage accumulation in the spleen. Accumulation of marginal zone and red pulp macrophages was histologically and immunohistochemically confirmed. n-3 FA induced peripheral blood monocytosis and an aspecific increase in bone marrow cellularity. Postendotoxin circulating TNF concentrations were increased significantly in n-3 FA-fed mice compared with controls. Splenectomy did not abolish this increase in circulating TNF. However, after macrophage depletion through liposomal dichloromethylene-biphosphonate, circulating TNF was not detectable after endotoxin challenge. Circulating concentrations of CSF-1 did not differ between the various experimental groups. It is suggested that the cellular changes observed relate to increased constitutive production of TNF.

Animals↗