Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026916 (MAC)
 5,226 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the response of monocytes/macrophages (MO/MAC) to lipopolysaccharide (LPS) and interferon-gamma (IFN gamma) stimulation with respect to the expression of macrophage-specific products, i.e. macrophage-colony-stimulating factor (M-CSF), c-fms, c-sis, tissue factors, transforming growth factor-beta (TGF beta) and interleukin-8 (IL8) after in vitro infection with HIV. The expression of IL8 was strongly elevated in HIV-infected cells, peaking at 4 h after stimulation with LPS. At that time, the uninfected control showed only weak expression of IL8. Other products, e.g. tissue factor, c-fms, M-CSF and TGF beta were not modulated after stimulation. In contrast to IL8, the expression of c-cis was significantly lower in infected cells after stimulation with IFN gamma compared to uninfected control cells.
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PMID:Expression of macrophage products after in vitro infection of human monocytes/macrophages with HIV. 844 75

To gain insights into a possible immune defect predisposing to disseminated mycobacteria infection, we studied three of six surviving children with disseminated Mycobacterium avium complex infection, who had no recognized form of immunodeficiency. We used mycobacteria isolated from the patients and diphtheria, tetanus and pertussis vaccine (DTP) to study antigen-specific T lymphocyte responses. We observed that interferon-gamma (IFN-gamma) production by T cells in response to antigens (both mycobacteria and DTP) in these patients with disseminated infection was greatly impaired. This defect did not seem to be the result of T cell unresponsiveness, as phytohaemagglutinin (PHA) stimulation was able to induce high levels of IFN-gamma comparable to those seen in control patients with localized infection. Further experiments showed that peripheral blood mononuclear cells (PBMC) from patients with disseminated infection were able to present influenza haemagglutinin (HA) peptides to specific T cell clones. However, this ability was lost when the whole HA protein was used as source of antigen. Taken together, these observations support the notion that the primary immune defect in these patients with disseminated mycobacterial infection rests in the antigen-processing functions of their antigen-presenting cells (APC). These findings may provide clues to the wider problem of susceptibility to mycobacteria and other intracellular pathogens and have implications in designing therapy for these patients.
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PMID:Defective antigen processing associated with familial disseminated mycobacteriosis. 856 83

Transfer of an interleukin 2/interferon-gamma-secreting islet-specific CD4+ T-cell clone, BDC-6.9, in the immunodeficient NOD-scid mouse induces destruction of pancreatic beta-cells without help from host B-cells, CD4+ T-cells, or CD8+ T-cells. However, a second islet-specific T-cell clone, BDC-2.5, showing the same cytokine profile and T-cell receptor Vbeta expression as BDC-6.9 was not capable of inducing diabetes or insulitis in NOD-scid mice. Even though BDC-2.5 by itself readily induces diabetes in young unmanipulated NOD mice, cotransfer of CD8-enriched T-cells was required to induce disease in NOD-scid mice. Immunohistochemical staining of pancreatic lesions in young NOD mice receiving either BDC-2.5 or BDC-6.9 showed the presence of CD4+, CD8+, Vbeta4+, and MAC-1+ cells within the infiltrate, similar to infiltrates in lesions of spontaneously diabetic female NOD mice. In contrast, NOD- scid mice that received BDC-6.9 showed only the presence of CD4+Vb4+ T-cells and a large population of MAC-1+ cells in islet lesions. NOD-scid recipients of cotransferred BDC- 2.5/CD8+ splenic T-cells showed a small population of CD4+ T-cells and a larger population of CD8+ T-cells within the infiltrated islets, whereas no infiltrate was detectable in recipients of CD8+ splenocytes or BDC-2.5 alone. Our results suggest that at least two types of islet-specific CD4+ T-cell clones play a role in diabetes pathogenesis.
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PMID:Transfer of diabetes in the NOD-scid mouse by CD4 T-cell clones. Differential requirement for CD8 T-cells. 859 38

The role of some cytokines including tumour necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha), interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta) and interleukin-6 (IL-6) in the generation of immunosuppressive macrophages (M phi s) in host spleen cells of Mycobacterium avium complex (MAC)-infected mice was studied. M phi populations with potent suppressor activity against concanavalin A (Con A)-induced mitogenesis of splenocytes (SPCs) were elicited not only in euthymic but also in athymic nude mice during MAC infection. The suppressor M phi s are, therefore, inducible not only through a T-cell-dependent mechanism but also through T-cell-independent mechanism. However, MAC-induced M phi s of athymic mice displayed about four times lower suppressor activity than those of euthymic mice, indicating that mature T cells are important for M phi activation to the highly immunosuppressive state. Anti-TNF, anti-IFN-gamma, and anti-TGF-beta antibodies (Abs) but not anti-IL-6 Ab inhibited in vivo generation of MAC-induced immunosuppressive M phi s, and the neutralizing efficacy was in the order of anti-IFN-gamma Ab > anti-TNF Ab > anti-TGF-beta Ab. The effects of TNF-alpha, IL-1 alpha, IL-6, and IFN-gamma alone or combinations of them upon the acquisition of the suppressor activity by cultured splenic M phi s were studied. When normal splenic M phi s were treated with each cytokine for 3 days, TNF-alpha, IFN-gamma, and IL-1 alpha alone caused a slight elevation of their suppressive activity. Treatment of the normal M phi s with the combination of either TNF-alpha+IL-1 alpha or TNF-alpha+IFN-gamma yielded a marked increase in the suppressor activity, followed by IL-1 alpha+IFN-gamma. These findings indicate the important roles of TNF-alpha, IFN-gamma, and IL-1 alpha in the generation of MAC-induced suppressor M phi s.
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PMID:The role of tumour necrosis factor-alpha in combination with interferon-gamma or interleukin-1 in the induction of immunosuppressive macrophages because of Mycobacterium avium complex infection. 870 52

Prostanoids, including prostaglandin E2 (PGE2), suppress macrophage effector functions against Mycobacterium tuberculosis. PGE2 production by monocytes infected with Mycobacterium avium complex (MAC) and its effects on intracellular mycobacterial growth were examined. Freshly obtained monocytes from healthy subjects were stimulated with lipopolysaccharide or 10(7) organisms/mL of 4 MAC strains. PGE2 production in monocyte supernatants peaked at 48 h. Significantly higher levels of PGE2 were produced by monocytes infected with the mixed rough-smooth, flat, and transparent (SmT) morphotype strain 86m2096 (26.8 +/- 5.2 ng/mL) than by the more virulent LR114 SmT morphotype strain (2.4 +/- 0.6 ng/mL; P < .05, paired t test). When infected monocytes were incubated with 1 microgram/mL indomethacin (IM) for 2 days and then further stimulated with interferon-gamma, no effect on intracellular MAC growth was evident. IM increased tumor necrosis factor-alpha (1.7 +/- 0.4 vs. 2.3 +/- 0.3 ng/mL; P = .005, paired t test) but not interleukin-1 beta (8.2 +/- 1.7 vs. 8.7 +/- 2.1 ng/mL, P = .34) production by monocytes stimulated with lipopolysaccharide. These data suggest that MAC-induced PGE2 expression may modulate cytokine production and intracellular parasitism.
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PMID:Induction of prostaglandin E2 by human monocytes infected with Mycobacterium avium complex--modulation of cytokine expression. 884 20

The effects of macrophage stimulation with interferon-gamma (IFN-gamma) before or after infection on the intracellular growth of Mycobacterium avium complex (MAC) were investigated. Treatment of murine peritoneal macrophages before infection with IFN-gamma (50 U/ml) for 24 h and 48 h, but not for 72 h, was associated with 41% and 52% significant MAC growth inhibition, respectively. NG-monomethyl-L-arginine (NMA) did not affect the preinfection antimycobacterial activity of IFN-gamma, thus indicating that nitric oxide was not involved in this phenomenon. In contrast, treatment of macrophages with IFN-gamma (50 U/ml) for 24 h and 48 h after infection was ineffective, whereas treatment for 72 h caused some MAC growth promotion. The use of NMA suppressed the IFN-gamma-mediated MAC growth, suggesting that nitric oxide may affect postinfection microbicidal function of macrophages. These results suggest that activation of macrophages with IFN-gamma before or after infection may direct the course of the infection and that nitric oxide may be detrimental more than beneficial for MAC-infected macrophages.
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PMID:Bidirectional effects of IFN-gamma on growth of Mycobacterium avium complex in murine peritoneal macrophages. 919

Disseminated infection caused by organisms of Mycobacterium avium complex is common in acquired immune deficiency syndrome (AIDS) patients. M. avium is an intracellular bacterium that multiplies within macrophages. We examined the effect of M. avium infection on the T-helper cell response in C57/BL/6 black mice. At weekly intervals, CD4+ T-cells were isolated from spleens and lines were created. T-cell lines were exposed to sonicated M. avium in the presence of feeder cells and macrophages and the supernatant were collected to measure the concentrations of interferon-gamma (IFN-gamma and interleukin-10 (IL-10). Production of IFN-gamma in CD4+ T-cells obtained from uninfected mice did not vary significantly during the 5 weeks. Levels of IFN-gamma produced by T-cell lines of infected mice were similar to the control mice during the first 2 weeks but significantly reduced (approximately 30 ng/ml) thereafter. In contrast, production of IL-10 by T-cell lines of infected mice was in a range of 190 to 342 pg/ml in weeks 1, 2 and 3, but increased to an average of 1300 pg/ml at weeks 4 and 5. Pre-immunized mice, when infected with M. avium strain 101, showed a different profile of T-cell cytokines, with high IFN-gamma and low IL-10 production. Proteins purified from a number of disease-associated (D-A) and non-D-A strains of M. avium were tested for the ability to induce IL-10. 65,000 MW and 60,000 MW proteins of M. avium induced significantly more IL-10 than 45,000 MW, 33,000 MW and 27,000 MW proteins. These results showed that M. avium predominantly stimulates either Th1 or Th2 T-helper cells according to the phase of the infection.
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PMID:Mycobacterium avium infection in mice is associated with time-related expression of Th1 and Th2 CD4+ T-lymphocyte response. 930 31

Mycobacterium avium complex infections (MAC) are being reported with increasing frequency in immunocompromised patients. When these infections become resistant to standard antibiotic therapy, treatment with interferon-gamma (IFN-gamma) can be helpful. Pain, fever, splenic enlargement, and cytopenias caused by splenic sequestration developed during IFN-gamma treatment in a 9-year-old boy and were successfully treated by splenectomy. The development of IFN-gamma-induced splenic sequestration and cytopenias in MAC-infected patients represents a new indication for splenectomy.
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PMID:Splenectomy in a child with chronic Mycobacterium avium complex infection and splenic sequestration. 960 93

Phagocytic cells with macrophage or dendritic cell phenotype, able to capture and ingest tumor cells, were derived in large numbers from peripheral blood mononuclear cells using two different activation procedures. Peripheral blood mononuclear cells were stimulated in nonadherent conditions in the presence of human AB serum with either granulocyte-macrophage colony-stimulating factor and dihydroxy-vitamin D3 for 7 days and with interferon-gamma for the last 18 hours to obtain activated macrophages (MAK) or with granulocyte-macrophage colony-stimulating factor and interleukin-13 for 7 days (with fresh interleukin-13 added on day 4) to obtain macrophage-dendritic cells (MAC-DC). A strong ability of MAC-DC to phagocytose yeasts was observed, in contrast to a low-intermediate phagocytosis capacity by MAK. Both CD14+ FCgammaR+ (FcgammaRI/CD64, FcgammaRII/CD32, FcgammaRIII/CD16) MAK and CD1a+/CD86+, CD14- MAC-DC were able to phagocytose whole tumor cells. However, only MAK phagocytosis was enhanced by FcgammaR engagement. MAK but not MAC-DC could lyse tumor cell in antibody-dependent cell cytotoxicity assays, via FcgammaRI. Thus, MAK as well as MAC-DC may represent valuable tools for different in vivo therapy strategies that do or do not include the use of monoclonal antibodies.
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PMID:Generation of phagocytic MAK and MAC-DC for therapeutic use: characterization and in vitro functional properties. 1021 Mar 33

We have described previously a family with an apparent genetic susceptibility to disseminated Mycobacterium avium complex infection and an underlying defect in IL-12 regulation leading to abnormally low interferon-gamma production. Their T cells appear to act normally when in the presence of normal accessory cells. Cell-to-cell contact was necessary for normal monocytes to complement the familial patient monocyte defect, suggesting the familial defect in interferon-gamma costimulation involves pathways requiring cell surface molecule interactions. In an effort to better characterize the abnormality in these patients, we examined the role of known costimulatory molecules in residual costimulation by patient PBMC compared to normals. Whereas normals utilized CD40/CD40L interactions and IL-12 production for optimal interferon-gamma costimulation in PHA-stimulated cocultures, familial patient interferon-gamma production was low and unaffected by their blockade. CD86 blockade caused a greater than 50% reduction in both normal and familial patient interferon-gamma production, implying that a majority of residual familial patient costimulation required this pathway. Furthermore, selected myelomonocytic cell lines (K562 and THP1) acted as potent accessory cells for interferon-gamma production by familial patient and normal T cells, largely independent of IL-12 production. However, CD86 blockade of K562 cell/familial cell cocultures resulted in less than a 20% reduction in interferon-gamma production, indicating that familial patient cells respond to IL-12- and CD86-independent costimulatory signals for interferon-gamma as well. Thus, we demonstrate that the familial defect also involves interferon-gamma costimulation pathways requiring both CD40/CD40L interaction and IL-12 production, while residual pathways remain that allow low-level interferon-gamma production. Familial Mycobacterium avium patient monocytes and certain myelomonocytic cell lines can be exploited to investigate IL-12-independent costimulation for interferon-gamma production.
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PMID:IL-12-Independent costimulation pathways for interferon-gamma production in familial disseminated Mycobacterium avium complex infection. 1022 16


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