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At least 757 records · Page 42Linked to original sources
PubMed1994

Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) or tumour necrosis factor-alpha (TNF-alpha) activate human alveolar macrophages to inhibit growth of Mycobacterium avium complex.

We investigated the effects of certain macrophage-active cytokines on the phagocytosis and growth inhibition of Mycobacterium avium complex (MAC) by human alveolar macrophages (AM). We also evaluated the effects of pretreatment with each cytokine on the superoxide anion release (O2-) from AM. The cytokines that we used were recombinant GM-CSF, natural type TNF-alpha, recombinant interferon-gamma (IFN-gamma), and recombinant IL-2. We found that phagocytosis by the various cytokine-stimulated AM was similar to that of unstimulated AM. On the other hand, significant growth inhibition of MAC was observed in the macrophages treated with GM-CSF or TNF-alpha, while no growth inhibition of MAC was observed in the macrophages treated with IFN-gamma or IL-2. Pretreatment with all cytokines tested enhanced the O2- release from AM, but there was no correlation between the enhancement of O2- release and the growth inhibition of MAC. Thus, we concluded that GM-CSF or TNF-alpha could activate AM to inhibit growth of MAC, probably not through the enhanced production of reactive oxygen intermediates.

Adult↗
PubMed1994

Effect of in vivo macrophage colony-stimulating factor on fungistasis of bronchoalveolar and peritoneal macrophages against Cryptococcus neoformans.

Macrophage colony-stimulating factor (M-CSF) given subcutaneously at a dose of 2.5 mg/kg of body weight (4.75 x 10(6) U/kg) to CD-1 male mice 8 to 12 weeks old was found to enhance significantly the fungistasis of bronchoalveolar macrophages (BAM) against Cryptococcus neoformans. When M-CSF was given 1, 3, 7, 9, or 13 days before an ex vivo challenge with C. neoformans, fungistasis was increased (P ranged from < 0.05 to < 0.001) compared with that induced by control BAM. A maximum effect was seen by days 1 and 3 after administration of M-CSF. Twenty-one days after M-CSF, BAM did not produce significantly enhanced fungistasis. M-CSF also significantly enhances the fungistatic effect of peritoneal macrophages (PM) if given 1, 3, and 7 days prior to testing against C. neoformans in comparison with control PM (P ranged from < 0.05 to < 0.001). PM did not produce enhanced fungistasis 9 or 13 days after administration of M-CSF. These studies demonstrating in vivo enhancement of anticryptococcal activity of macrophages with M-CSF provide a rationale for in vivo use of M-CSF to enhance resistance to infection with C. neoformans.

Animals↗
PubMed1994

Expression and regulation of macrophage inflammatory protein-1 alpha by murine alveolar and peritoneal macrophages.

A number of disease states are characterized by the accumulation of inflammatory cells at the site of tissue injury. Mononuclear phagocytes (M phi) represent key cellular mediators of inflammation via the production of regulatory and chemokinetic cytokines. One such cytokine, macrophage inflammatory protein-1 alpha (MIP-1 alpha), has been shown to be one of the major inducible chemotaxins expressed from murine macrophage cell lines (RAW 264.7). We postulated that MIP-1 alpha is a major monocyte chemoattractant produced by resident M phi, and the magnitude of production of this chemotaxin may depend upon the specific population of M phi studied. To test this hypothesis, we isolated alveolar macrophages (AM phi) and peritoneal macrophages (PM phi) from CD-1 mice by bronchoalveolar and peritoneal lavage, respectively. Recombinant murine MIP-1 alpha accounted for significant neutrophil chemokinetic rather than chemotactic activity, as assessed by checkerboard analysis. LPS-stimulated AM phi-derived monocyte chemotactic activity (MCA) was significantly neutralized by specific rabbit anti-murine MIP-1 alpha serum. In contrast, PM phi-derived conditioned media failed to produce MCA attributable to MIP-1 alpha. The production of MIP-1 alpha was then characterized from both AM phi and PM phi. While unstimulated AM phi and PM phi failed to express MIP-1 alpha mRNA, both AM phi and PM phi challenged with lipopolysaccharide (LPS) expressed MIP-1 alpha mRNA in a time-dependent fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Alterations of ambient oxygen tension modulate the expression of tumor necrosis factor and macrophage inflammatory protein-1 alpha from murine alveolar macrophages.

Tissue injury that occurs as a result of ischemia and subsequent reperfusion is characterized by endothelial cell injury, edema formation, and the influx of inflammatory leukocytes. Two macrophage-derived proinflammatory cytokines which may play a critical role in cellular injury and leukocyte recruitment/activation that occurs in the setting of ischemia-reperfusion injury are tumor necrosis factor alpha (TNF) and macrophage inflammatory protein-1 alpha (MIP-1 alpha). To determine if modulation of ambient oxygen tensions in vitro alters the expression of proinflammatory cytokines from activated macrophages, murine alveolar macrophages (AMO) were cultured in various combinations of ambient oxygen concentrations, then the supernatant fluid and cell pellet assayed for the presence of TNF and MIP-1 alpha messenger RNA (mRNA) and protein. We demonstrated that conditions of anoxia (95% nitrogen/5% CO2) or hyperoxia (95% oxygen/5% CO2) independently resulted in the increased expression of both TNF and MIP-1 alpha mRNA and protein from lipopolysaccharide (LPS)-stimulated AMO, as compared with cells cultured in room air. The specific culture condition of anoxia (x 6 h) followed by hyperoxia (x 18 h) produced the greatest increases in both TNF and MIP-1 alpha, suggesting that when following a period of anoxic priming, oxygen stress results in exaggerated cytokine production. A period of at least 4.5 to 6 h of anoxia prior to hyperoxic exposure was found to be the minimal time required for anoxic priming. Furthermore, the coincubation of LPS-treated AMO with dimethyl sulfoxide (DMSO) attenuated the anoxia-hyperoxia-induced increases in TNF and MIP-1 alpha mRNA by 23% and 34%, respectively. These findings suggested that alterations in ambient oxygen tension can regulate the expression of TNF and MIP-1 alpha from activated AMO, and that oxidant-related cytokine production may represent an important mechanism by which inflammation occurs in the clinical settings of ischemia-reperfusion injury and hyperoxia.

Animals↗
PubMed2006

Induction of tumour necrosis factor receptor-expressing macrophages by interleukin-10 and macrophage colony-stimulating factor in rheumatoid arthritis.

Despite its potent ability to inhibit proinflammatory cytokine synthesis, interleukin (IL)-10 has a marginal clinical effect in rheumatoid arthritis (RA) patients. Recent evidence suggests that IL-10 induces monocyte/macrophage maturation in cooperation with macrophage-colony stimulating factor (M-CSF). In the present study, we found that the inducible subunit of the IL-10 receptor (IL-10R), type 1 IL-10R (IL-10R1), was expressed at higher levels on monocytes in RA than in healthy controls, in association with disease activity, while their expression of both type 1 and 2 tumour necrosis factor receptors (TNFR1/2) was not increased. The expression of IL-10R1 but not IL-10R2 was augmented on monocytes cultured in the presence of RA synovial tissue (ST) cell culture supernatants. Cell surface expression of TNFR1/2 expression on monocytes was induced by IL-10, and more efficiently in combination with M-CSF. Two-color immunofluorescence labeling of RA ST samples showed an intensive coexpression of IL-10R1, TNFR1/2, and M-CSF receptor in CD68+ lining macrophages. Adhered monocytes, after 3-day preincubation with IL-10 and M-CSF, could produce more IL-1beta and IL-6 in response to TNF-alpha in the presence of dibutyryl cAMP, as compared with the cells preincubated with or without IL-10 or M-CSF alone. Microarray analysis of gene expression revealed that IL-10 activated various genes essential for macrophage functions, including other members of the TNFR superfamily, receptors for chemokines and growth factors, Toll-like receptors, and TNFR-associated signaling molecules. These results suggest that IL-10 may contribute to the inflammatory process by facilitating monocyte differentiation into TNF-alpha-responsive macrophages in the presence of M-CSF in RA.

Adult↗
PubMed2000

Phosphatidylinositol-3' kinase-dependent vesicle formation in macrophages in response to macrophage colony stimulating factor.

Treatment of the BAC1.2F5 macrophage cell line with Macrophage Colony Stimulating Factor (M-CSF) resulted in a rapid induction of vesiculation that was reminiscent of macropinocytosis. Time-lapse micrography showed that these vesicles initiated as small vesicles at the cell periphery, but grew in size and migrated with time to a perinuclear localisation after growth factor stimulation. Immunofluorescence showed that the M-CSF receptor (c-fms) associated with the small vesicles and also the larger phase-bright vesicles. Treatment with two distinct inhibitors showed that the rapid initiation of vesicle formation was not dependent on phosphatidylinositol-3' (PI-3) kinase activity; however, the subsequent maintenance, maturation and translocation of the large, phase-bright, c-fms-containing vesicles was dependent on PI-3 kinase activity. The inhibitors could also reverse the further maturation of preformed vesicles. The inhibition of vesicle trafficking and maturation correlated with ablation of M-CSF-induced PI-3 kinase activity associated with p110(alpha). These data demonstrate a role for PI-3 kinase in vesicle trafficking and maintenance. PI-3 kinase activity was also necessary for the macropinocytotic response in macrophages, a process that is essential for efficient antigen processing and presentation in macrophage-like cells.

Animals↗
PubMed1985

Studies on macrophage-activating factor (MAF) in antitumor immune responses. I. Tumor-specific Lyt-1+2- T cells are required for producing MAF able to generate cytolytic as well as cytostatic macrophages.

In the present study we investigated some of the cellular mechanisms for the generation of macrophage-activating factor(s) (MAF) in immune responses to tumor antigens. C3H/HeN mice were immunized to syngeneic MH134 hepatoma or MCH-1-A1 fibrosarcoma by intradermal inoculation of viable tumor cells, followed by the surgical resection of the tumor. Spleen and lymph node cells from these tumor-immune mice were stimulated in vitro with the corresponding tumor cells, and supernatant from such a culture was tested for an ability to activate macrophages to exert their cytostatic and cytolytic activities as detected on tumor cells unrelated to immunizing tumors. Peritoneal adherent cells as a macrophage source, which were preincubated with supernatant from co-culture of tumor-unimmunized normal spleen and lymph node cells plus tumor cells, failed to exhibit any significant antitumor effect on unrelated X5563 tumor cells, whereas the addition of supernatant from cultures containing immune lymphocytes to adherent cells resulted in appreciably potent cytostatic and cytolytic effects on X5563 tumor cells, indicating the generation of MAF in culture supernatant. The activation of tumor-immune spleen and lymph node cells for MAF generation was tumor-specific, because anti-MH134- and anti-MCH-1-A1-immune lymphocytes produced MAF by the stimulation with the respective but not with the other alternative tumor cells. Such MAF production was abolished by treatment of tumor-immune spleen and lymph node cells with anti-Thy-1.2 or anti-Lyt-1.1 but not with anti-Lyt-2.1 antibody plus complement before culturing. These results indicate that the tumor-specific Lyt-1+2- T cell subset has a crucial role in generating MAF by which an adherent cell population as a source of macrophages acquires the potential for inducing a cytolytic as well as a cytostatic effect on tumor cells.

Animals↗
PubMed1996

Modulation of phagocytosis by anisoosmolarity and betaine in rat liver macrophages (Kupffer cells) and RAW 264.7 mouse macrophages.

Hypoosmotic exposure (205 mosmol/l) of rat liver macrophages (Kupffer cells) for 12 h stimulated phagocytosis of latex particles by about 20%, whereas hyperosmotic exposure (405 mosmol/l) resulted in 30-40% inhibition. Inhibition of phagocytosis by hyperosmolarity was fully prevented in the presence of betaine, which acts as an osmolyte in liver macrophages. When hyperosmotically exposed Kupffer cells were preloaded with betaine, induction of phagocytosis by addition of latex particles led to the stimulation of betaine efflux from the cells. Stimulation of phagocytosis also inhibited the hyperosmolarity-induced cumulative uptake of betaine into Kupffer cells, but did not prevent the hyperosmolarity-induced increase in BGT1-mRNA levels. Whereas these findings suggest an involvement of cell volume and betaine in the regulation of phagocytosis in Kupffer cells, betaine transport was not affected upon induction of phagocytosis in RAW 264.7 mouse macrophages. The findings are compatible with a role of betaine in maintaining cell volume homeostasis during phagocytosis in Kupffer cells, but not in RAW 264.7 mouse macrophages. This may be relevant for the maintenance of liver hemodynamics, since volume changes of liver macrophages following ingestion of phagocytozable material might otherwise impair sinusoidal perfusion.

Animals↗
PubMed1993

Membrane-associated C-reactive protein on rat liver macrophages is synthesized within the macrophages, expressed as neo-C-reactive protein and bound through a C-reactive protein-specific membrane receptor.

We could recently show that rat liver macrophages (Kupffer cells) express a membrane-bound form of C-reactive protein on their surface. Because it is removed by washing the cells in buffers containing Ca(++)-chelators, membrane-bound C-reactive protein is a peripheral protein rather than an integral part of the Kupffer cell membrane. This Kupffer cell membrane-bound C-reactive protein is identical to the galactose-specific particle receptor previously characterized. We now present evidence that Kupffer cells do not acquire soluble serum C-reactive protein but synthesize their own membrane-bound C-reactive protein. By RNA-RNA in situ hybridization, it was found that hepatocytes are not the only sort of liver cells synthesizing C-reactive protein, but C-reactive protein-specific mRNA is present also in Kupffer cells. During acute-phase response C-reactive protein mRNA is found in increased amounts within liver macrophages too. Furthermore, by labeling experiments with antisera against native, pentameric soluble serum C-reactive protein and monoclonal antibodies against a neoepitope present on C-reactive protein subunits only, we could establish that the membrane-bound C-reactive protein expressed on the liver macrophage is not the pentameric molecule of soluble serum C-reactive protein, but rather consists of C-reactive protein subunits. Finally, we present evidence that liver macrophages contain a binding protein in their plasma membrane, with an apparent molecular weight of 59 to 61kD, specific for C-reactive protein and similar to the one previously isolated from macrophage cell lines.

Animals↗
PubMed1998

Human macrophages induced in vitro by macrophage colony-stimulating factor are deficient in IL-12 production.

IL-12 is important for Th1 differentiation. Myeloid-derived antigen-presenting cells (APC) such as monocytes, macrophages (Mphi) and dendritic cells (DC) are believed to be major sources of IL-12 in vivo. We have compared IL-12 production of fresh monocytes with Mphi differentiated in vitro using macrophage colony-stimulating factor (M-CSF) or human plasma, and in vitro generated dendritic cells, since these differentiated cell types represent APC at sites of antigen challenge. Macrophages stimulated with lipopolysaccharide (LPS) or heat-killed Listeria monocytogenes in the presence or absence of IFN-gamma produced minimal IL-12 p70 by comparison with DC or monocytes, despite comparable production of TNF-alpha. M-CSF-induced Mphi produced low levels of IL-10 constitutively and high levels after stimulation with LPS, but neutralization of IL-10 did not augment Mphi IL-12 production. Exposure of Mphi to TNF-alpha, granulocyte-macrophage CSF or IFN-gamma did not substantially up-regulate IL-12. Therefore M-CSF induces a differentiated Mphi phenotype in which IL-12 production is down-regulated, perhaps irreversibly. This may be the default pathway for monocyte-Mphi development in the absence of inflammation.

Cell Differentiation↗
PubMed1991

Colony stimulating factor-1 stimulates diacylglycerol generation in murine bone marrow-derived macrophages, but not in resident peritoneal macrophages.

Colony stimulating factor-1 (CSF-1) stimulates DNA synthesis in murine bone marrow-derived macrophages (BMM); however, unlike BMM, murine resident peritoneal macrophages (RPM) undergo a poor proliferative response. It has previously been shown that phosphatidylinositol-4,5-bisphosphate hydrolysis is not associated with CSF-1 action in BMM. In this report we demonstrate that, despite a lack of inositol trisphosphate generation, CSF-1 transiently elevated both [3H]myristoyl- and [3H]arachidonyl-diacylglycerol (DAG) in BMM in a dose-dependent fashion. CSF-1 failed, however, to stimulate an increase in either species of DAG in RPM. Thus, DAG could be a second messenger for the proliferative action of CSF-1 in macrophages. Other mitogenic agents, 12-0-tetradecanoyl phorbol 13-acetate (TPA) and exogenous phospholipase C, also increased BMM levels of [3H]myristoyl- and [3H]arachidonyl-DAG. The nonmitogenic agents, lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha) and zymosan, had different effects on the generation of either species of DAG in BMM. LPS failed to elevate either form, TNF-alpha increased only [3H]arachidonyl-DAG, while zymosan stimulated levels of both species of DAG. It therefore appears that increased diacylglycerol generation may be necessary, but perhaps not sufficient, for macrophage proliferation.

Animals↗
PubMed1984

Effect of lidocaine on production of migration inhibitory factor and on macrophage motility: in vitro exposure of guinea pig lymphocytes and macrophages.

Exposure of lymphocytes from guinea pigs sensitized to keyhole limpet hemocyanin and of macrophages from nonsensitized animals to noncytotoxic doses of lidocaine (10(-4) to 10(-6) M) resulted in the inhibition of the production of macrophage migration inhibitory factor and of macrophage motility. The inhibition of both processes was related to the concentration of lidocaine in the medium. The effects of lidocaine, a membrane-stabilizing drug, were apparently related to its ability to interact with the cell surface and cause changes in the surface ionic configuration of the cells, as determined by cell electrophoresis. The drug conferred permanent changes in the surface of lymphocytes at all concentrations tested, but the changes in the surface of macrophages induced in the presence of 10(-5) and 10(-6) M of the drug were reversible. The presence of noncytotoxic doses of lidocaine in the cellular environment resulted in significant changes in cellular functions that appeared to be related to the ability of the drug to interact with cell membranes in a manner determined by the specific surface properties of the cell.

Animals↗
PubMed1995

Enhancement in accessibility to macrophages by modification of mucin-type carbohydrate chains on a tumor cell line: role of a C-type lectin of macrophages.

We investigated the role of mucin-type (O-linked) carbohydrate chains of tumor target cells in the recognition by macrophages through a Gal/GalNAc-specific calcium-dependent lectin. Binding of a soluble form of this lectin to P815 mastocytoma cells was increased by treatment with benzyl-GalNAc, which presumably inhibited the extension of mucin-type carbohydrate chains. The levels of cell surface expression of GalNAc residues were elevated after benzyl-GalNAc treatment, as revealed by the binding of Vicia villosa agglutinin B4 and Dolichos biflorus agglutinin. Adhesion of treated P815 cells to this lectin immobilized on plastic surfaces also increased. Furthermore, the binding of P815 cells to macrophage-like RAW 264.7 cells and to peritoneal macrophages also increased after the same treatment. We concluded that elevated levels of cell surface terminal GalNAc in mucin-type carbohydrate chains increased accessibility of P815 cells to macrophages through Gal/GalNAc-specific calcium-dependent lectins.

Acetylgalactosamine↗
PubMed1994

Alterations in macrophage signal transduction pathways mediate post-traumatic changes in macrophage function.

After injury, macrophage effector function diminishes while suppressor function increases. Protein kinase C (PKC), which initiates superoxide synthesis and phagocytosis, and phospholipase A2 (PLA2), which initiates eicosanoid metabolism, are key enzymes in cell signal transduction, which may mediate this change in cell function. The aim of this study was to investigate the effect of trauma on macrophage signal transduction. Swiss-Webster (CFW) mice (n = 210) were randomized to control or hindlimb amputation groups. Animals were sacrificed 24 hr after injury. Peritoneal macrophage function was assessed by measurement of superoxide anion (O2-), Fc, mannose-fucose-mediated phagocytosis, and PGE2 release. Membrane and cytosolic PKC activity were measured by radioimmunoassay in unstimulated and phorbol ester-stimulated cells. Membrane fatty acids and PLA2 activity were measured by thin-layer chromatography. Hindlimb amputation resulted in significantly decreased superoxide anion synthesis (0.7 +/- 0.2 nm vs 1.7 +/- 0.3 nmol/l/10(6) cells in controls, P < 0.01) and phagocytosis and a significant increase in prostaglandin E2 synthesis. This was associated with a shift in cell membrane metabolism with increased PLA2 activity, arachidonic acid turnover, and a significant reduction in PKC membrane translocation in response to phorbol ester. Together these data demonstrate an alteration in signal transduction pathways, which may account for the observed change in macrophage function after injury.

Amputation, Surgical↗
PubMed1993

Production of cytokines and PGE2 and cytotoxicity of stimulated bone marrow macrophages after thermal injury and cytotoxicity of stimulated U-937 macrophages.

Bone marrow-derived macrophages from normal and burned rats were cultured for one and four days in the presence of LPS, PHA, or opsonized zymosan as activators, and the supernatants were assayed for the inflammatory mediators TNF, IL-6, and PGE2 and the cells assayed for cytotoxicity. The macrophages responded differently to the various stimuli regarding cytotoxicity and the production of mediators, perhaps implicating the complement receptor CR1 in TNF production and the LPS receptor CD14 or the PHA lectin receptor in IL-6 and PGE2 production and for cytotoxicity. The response of the cells also depended on culture time and postburn time; in addition, macrophages from burned and unburned animals responded differently, depending on postburn day and the type of stimulus. TNF production was generally higher for one-day compared to four-day cultures (i.e., TNF was disappearing in the cultures), but IL-6 and PGE2 production was greater in four-day cultures. The results of this study suggest that thermal injury can contribute to the development of inflammatory and cytotoxic macrophages from bone marrow progenitor cells.

Animals↗
PubMed1992

Developmental regulation of granulocyte-macrophage colony-stimulating factor production during human monocyte-to-macrophage maturation.

Cells of the macrophage lineage are a major source of various cytokines and hematopoietic growth factors. With regard to the growth factors acting on cells of their own lineage, macrophage colony-stimulating factor (M-CSF) has been proven to be secreted by monocytes (MO) and macrophages (MAC), whereas the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by human MO/MAC is under debate. Here we report that in elutriation-purified MO, as well as in MAC derived from cultured MO, GM-CSF m-RNA was regularly induced by LPS. In MO the GM-CSF message was still detectable 18 h after stimulation under serum-free conditions, but in contrast was already lost at this time point in MAC. Secreted GM-CSF protein was detected in the culture medium using a sandwich ELISA. Furthermore, a factor-dependent cell line (M-07) was used for a biological assay. Here, a neutralizing anti GM-CSF antibody specifically blocked the proliferation-inducing activity of MO/MAC supernatants. Whereas only small amounts of GM-CSF were detected in MO, its secretion increased severalfold upon MO-to-MAC differentiation in vitro. A similar increase upon in vitro maturation of MO was observed for the production of granulocyte colony-stimulating factor. The highest amounts of GM-CSF (up to 2.8 ng/10(6) cells) were produced by MAC that had been derived from MO cultured under serum-free conditions in the presence of 0.5 mg/ml albumin as the only medium supplement.

Blotting, Northern↗
PubMed1993

Muramyldipeptide and granulocyte-macrophage colony-stimulating factor enhance interferon-gamma-induced nitric oxide production by rat alveolar macrophages.

Rat alveolar macrophages incubated with recombinant rat interferon-gamma produce L-arginine-dependent nitric oxide, which is rapidly decomposed into nitrite: this production by interferon-gamma was markedly enhanced by granulocyte-macrophage colony-stimulating factor and muramyldipeptide, but not by other cytokines. The enhancement was dependent on the presence of L-arginine in the incubation medium. It was based on a simple synergism between interferon-gamma and muramyldipeptide and a priming effect of granulocyte-macrophage colony-stimulating factor for interferon-gamma-induced nitrite production. These data suggest that cytokine networks are important in the induction of nitric oxide in rat alveolar macrophages.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1998

Effects of macrophage migration inhibitory factor and macrophage migration stimulatory factor on function and survival of foetal dopaminergic grafts in the 6-hydroxydopamine rat model of Parkinson's disease.

Activated microglia play an important role in the rejection of intracerebral grafts and the degeneration of axotomized neurones. We studied the effect of macrophage migration stimulatory factor (MSF) or macrophage migration inhibitory factor (MIF) on allogeneic foetal mesencephalic dopaminergic grafts transplanted into the striatum of 6-hydroxydopamine-lesioned rats. Rotation testing revealed a significant compensation of lesion-induced motor asymmetry 3 weeks post-grafting in animals treated with MIF and vehicle-treated controls compared with pre-graft values (Student's t-test, P < or = 0.005) and MSF-treated animals (ANOVA, post hoc Fisher PLSD test, P < or = 0.05). The MSF group showed no significant compensation. Graft recipients with MIF application (1452.06 +/- 164.32 tyrosine hydroxylase-positive ventral mesencephalic cells) and controls (1753.21 +/- 165.51 tyrosine hydroxylase-positive neurones) displayed good graft survival. Animals with MSF application showed a significant reduction of tyrosine hydroxylase-positive grafted cells (MSF 570.36 +/- 209.49 cells) and graft volumes compared with the MIF and the control group (ANOVA, post hoc Fisher PLSD test, P < or = 0.05). The proportional area of microglia was significantly reduced in MIF animals compared with control animals (ANOVA, post hoc Fisher PLSD test, P < or = 0.001). Activated microglia and macrophages were reduced by half in the MIF-treated group compared with MSF animals and controls. We conclude that intrastriatal injections of MSF result in impaired function and survival of allogeneic ventral mesencephalon (VM) grafts 3 weeks after transplantation. MIF can reduce the number of microglia and macrophages in allogeneic foetal VM grafts. A reduction of microglia via MIF application did not enhance graft function and survival.

Animals↗