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)

The macrophage is an essential component of the host defense against intracellular pathogens including MAC. Especially alveolar macrophages act as a first line defense in the lungs against MAC infection. Some cytokines were reported to activate mouse peritoneal macrophages and human monocyte-derived macrophages to inhibit growth or kill MAC. But we could find only one report describing the effect of cytokines on anti-MAC activities of human alveolar macrophages (PAM). Thus, we investigated the effect of several cytokines on anti-MAC activities of PAM. PAM were recovered from 12 healthy subjects by bronchoalveolar lavage and cells were cultured in RPMI 1640 with 10% heat-inactivated human AB serum. After 2 hours incubation nonadherent cells were discarded by vigorous washing to from monolayers of PAM (2 x 10(5) PAM in each 11-mm diameter tissue culture dish). Then we added 2 x 10(6) viable MAC bacteria (31F093T) and each cytokine to the wells simultaneously. We prepared the well without cytokines as control. After 96 hours incubation, PAM were disrupted by sonication, then all bacteria that had located inside and outside of the cells were plated onto 7H10 agar. The results are reported as mean colony forming units per each well. We had determined the optimal dose of each cytokine to prime PAM for enhanced O2- release and we used that optimal dose in this experiment. PAM with TNF-alpha pretreatment, and PAM with IFN-gamma pretreatment could release increased amount of O2- significantly, compared with control. PAM with IL-2 pretreatment and PAM with GM-CSF pretreatment also released somewhat increased amount of O2-.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of cytokines on anti-Mycobacterium avium complex (MAC) activities of human alveolar macrophages]. 154 9

An effective intracellular concentration of an antimicrobial agent is essential for therapy of infections caused by organisms of the Mycobacterium avium complex. We previously reported on the effect of the combination of azithromycin and tumor necrosis factor (TNF) against M. avium infection in macrophages. We now report that stimulation of macrophages either with recombinant human gamma interferon (IFN-gamma, 10(2) U/ml) or with recombinant human TNF-alpha (10(2) U/ml) resulted in an increase in the intracellular concentration of azithromycin by approximately 200% within 3 h, compared with the concentration in unstimulated macrophages. Infection of macrophages with M. avium complex led to a decrease in the uptake of [14C]azithromycin by infected cells, compared with that by uninfected controls. Stimulation of infected macrophages with recombinant IFN-gamma or TNF-alpha overcame the inhibitory effect associated with infection. These results suggest that the increased bactericidal activity of the TNF-alpha-azithromycin or IFN-gamma-azithromycin combination against M. avium is related to enhanced uptake of the antibiotic by the stimulated phagocyte.
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PMID:Stimulation with cytokines enhances penetration of azithromycin into human macrophages. 166 56

The long term survival of peripheral blood derived human macrophages (M phi) from normal, healthy donors after infection with Mycobacterium avium intracellulare (MAI) correlates with the increased induction of TNF-alpha and IL-6 mRNA and protein by the infected M phi. This conclusion is based on the following observations: M phi from approximately 30% of the blood donors in our study die 3 to 4 days after inoculation (MAI-growth nonsupportive (NS], whereas M phi from the other donors survive inoculation with MAI for 7-10 days (MAI-growth supportive (S)). S-type M phi when infected with MAI had markedly increased amounts of TNF-alpha and IL-6 mRNA and protein when compared to NS-type M phi. The effect of LPS on the induction of TNF-alpha mRNA and protein was also significantly enhanced in S-type M phi in comparison to NS cells. In contrast, IL-1 beta mRNA and protein production had similar increases in both donor types when infected with MAI or stimulated with LPS. The phenotype of the donors in the amount of TNF-alpha and IL-6 produced in response to MAI infection remained stable for a period of more than 1 yr. Pretreatment of NS M phi with recombinant human granulocyte-macrophage-CSF, but not IFN-gamma, however, converted NS M phi into a S-type cell phenotype. These granulocyte-macrophage-CSF pretreated NS M phi survived infection with MAI for a longer period of time and also had increased production of both TNF-alpha and IL-6 mRNA and protein. Cultures of S-type M phi infected with MAI had higher numbers of intracellular bacteria when compared to cultures of NS-infected M phi. Thus, increased survival of MAI-infected human M phi in vitro is correlated to increased production of TNF-alpha and IL-6 in response to infection with MAI.
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PMID:Survival of human macrophages infected with Mycobacterium avium intracellulare correlates with increased production of tumor necrosis factor-alpha and IL-6. 194 Mar 76

In order to verify the participation of some cytokines in the expression of the suppressor activity of splenic macrophages (M phi s) induced by Mycobacterium avium complex (MAC) infection, we studied whether anticytokine antibodies were capable of blocking their suppressor activity against concanavalin A (ConA)-induced mitogenesis of splenocytes (SPCs). When either anti-tumor necrosis factor (TNF), anti-transforming growth factor-beta (TGF-beta), or anti-interferon-gamma (IFN-gamma) antibody was added to culture medium, suppressor activity was markedly reduced, in the order of anti-TNF, anti-IFN-gamma, and anti-TGF-beta antibodies. By contrast, neither anti-interleukin-6 (IL-6) nor anti-IL-10 antibody exerted such a blocking effect. Therefore, TNF, IFN-gamma, and TGF-beta seem to be related to the full display of the suppressor function of MAC-induced M phi s. However, TNF-alpha and IFN-gamma but not TGF-beta were substantially lacking in inhibitory action against SPC mitogenesis, when added exogenously. Hence, it is unlikely that TNF-alpha and INF-gamma directly modulated the proliferative response of T cells. On the other hand, both TNF-alpha and IFN-gamma potentiated the effector function of the suppressor M phi s. Because their suppressor activity was severely reduced by NG-monomethyl-L-arginine and aminoguanidine, nitric oxide (NO) synthase inhibitors, an NO-dependent mechanism is important for the expression of the immunosuppressive function of MAC-induced M phi s. Moreover, because these M phi s seem to produce a substantial amount of TNF-alpha in membrane-bound form, cell-to-cell contact might be needed for efficient expression of their suppressor action on target T cells.
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PMID:The role of tumor necrosis factor, interferon-gamma, transforming growth factor-beta, and nitric oxide in the expression of immunosuppressive functions of splenic macrophages induced by Mycobacterium avium complex infection. 749 69

Mycobacterium avium intracellulare (MAI) infection is a serious opportunistic infection that occurs in children with human immunodeficiency virus (HIV) infection. In MAI the hematologic system is profoundly affected. In the present study the hematologic manifestations of MAI in 37 HIV-infected infants and children were reviewed. Anemia was the predominant feature in all patients, with severe anemia (hemoglobin < 6 g/dL) occurring in 7 of 34 (21%) patients. This was followed by leukopenia (79%), monocytosis (82%), thrombocytopenia (59%), leukoerythroblastic reaction (68%), and neutropenia (41%). Serum tumor necrosis factor (TNF)-alpha was markedly elevated in all patients with MAI with an X +/- SE of 702 +/- 182 pg/mL. There was an association between elevated TNF-alpha and anemia in these patients.
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PMID:Elevated tumor necrosis factor-alpha in association with severe anemia in human immunodeficiency virus infection and Mycobacterium avium intracellulare infection. 764 Jan 75

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.
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PMID: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. 792 77

Although various antimicrobial drugs show appreciable bactericidal activity in the early phase (2 to 4 weeks after infection) of Mycobacterium avium complex (MAC) infections in mice, no drug, as far as we know, can continue to exert the growth inhibiting activity against the bacteria at the site of infection in the progressed stage. Here, we studied the mechanisms of the bacterial regrowth which usually starts around 2-4 weeks after infection. First, the changes in the level of TNF-alpha, IFN-gamma, IL-6 and IL-10 in the lungs and spleen during the course of MAC infections was examined. Tissue levels of TNF-alpha and IL-10 increased around weeks 2 to 4, then rapidly decreased thereafter, and returned to the normal levels by week 8, while levels of IFN-gamma and IL-6 remained very low throughout the observation period. In this experiment, the bacterial CFUs rapidly decreased during the first 2 weeks of the treatment with a rifamycin derivative, KRM-1648, and thereafter the regrowth of the organisms was observed even in mice treated continuously with KRM-1648, although the rate of bacterial growth in the treated mice was much lower than in untreated control mice. Second, effect of either anti-TGF-beta or anti-IL-10 antibody on intracellular growth of MAC in human monocytes cultured in vitro in the medium with or without addition of TNF-alpha or IFN-gamma were examined. Anti-TGF-beta and anti-IL-10 antibodies potently reduced the bacterial growth in monocytes. Effects of TNF-alpha and IFN-gamma in reducing the bacterial growth was potentiated by the addition of either anti-TGF-beta or anti-IL-10 antibody. Third, anti-IL-10 antibody augmented to some extent the chemotherapeutic efficacy of KRM-1648 against MAC infection, when the drug was given to mice at weeks 2 and 4 after infection. From these results, it is suggested that IL-10 derived from MAC-infected macrophages in response to stimulation with some bacterial components, such as lipoarabinomannan, might downregulate the antimicrobial function of host macrophages against MAC.
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PMID:[Mechanism of bacterial regrowth at the sites of infection in Mycobacterium avium complex-infected mice during treatment with chemotherapeutic agents]. 855 14

Mycobacterium avium complex (MAC) is an intracellular pathogen which causes disseminated bacterial infection in immunocompromised individuals. This organism predominantly infects macrophages. Attachment of MAC to macrophages is the first step prior to invasion. We have previously shown that a 70 kDa protein of M. avium (Ma) is one of nine monocyte-binding proteins. In the present study, we have purified this protein from sonic extracts of Ma and studied some of its properties. The N-terminal sequence of this protein was identified and found to exhibit a strong homology to the 70 kDa heat shock protein (hsp) of M. leprae (Ml) and M. tuberculosis (Mtb). This protein was found to be present on the surface of the organism and was able to inhibit the attachment of intact Ma to human monocyte derived macrophages (MDM) up to 49% in an in vitro attachment assay using intact fluorescein isothiocyanate (FITC)-labelled Ma. Bovine serum albumin (BSA) and recombinant 70 kDa hsp from Mtb, which were used as controls, inhibited this attachment by 9.8 and 18%, respectively. These results suggest that the 70 kDa protein may have a role in the attachment of intact Ma to MDM. When tested in lymphocyte activation assays, this protein did not appear to significantly stimulate proliferation. However, it was found to stimulate the production of tumor necrosis factor (TNF)-alpha by MDM. This protein may be one of several Ma antigens that trigger host immune response by binding to MDM and stimulating the production of inflammatory cytokines such as TNF-alpha by these cells.
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PMID:Isolation and characterization of a 70 kDa protein from Mycobacterium avium. 897 87

The pathophysiologic basis for the exuberant intracellular growth of Mycobacterium avium complex (MAC) in AIDS patients is unclear but may relate to altered expression of modulatory cytokines. Interleukin (IL)-1, IL-6, and TNF-alpha expression by monocytes from AIDS patients and healthy subjects (HS) stimulated with isogeneic MAC strains (SmT, smooth-transparent, virulent; SmD, smooth-domed, avirulent) was examined. Spontaneous cytokine production was not observed in patients with AIDS. MAC strains induced less IL-1 alpha and IL-1 beta release in AIDS patients than HS (P < 0.05). The ratio of cell-associated to supernatant IL-1 alpha also was increased in AIDS patients (P = 0.03). IL-1 beta mRNA expression paralleled protein release in either group of subjects. In both HS and AIDS patients, stimulation with SmD induced more IL-1 and TNF-alpha release by monocytes compared to SmT. In AIDS patients, SmD also induced greater IL-6 release than SmT (P < 0.01). Alterations in monocyte expression and compartmentalization of the regulatory cytokines IL-1 and IL-6 may enhance bacterial replication and contribute to the pathogenesis of MAC infection in AIDS.
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PMID:Altered IL-1 expression and compartmentalization in monocytes from patients with AIDS stimulated with Mycobacterium avium complex. 932 38

I have studied pathogenesis of pulmonary Mycobacterium avium complex disease (PMAC), using mouse and human alveolar macrophage (PAM) model of the infection as well as clinical evaluations. The mouse model revealed no relation between natural resistance against the bacteria and the activation of macrophages which was evaluated on the basis of releasing capacities of prostaglandin E2 and superoxide anion. The PAM model suggested that TNF-alpha and GM-CSF could activate PAM to restrict the intracellular growth of the bacteria, probably not through the superoxide anion release, but through the myeloperoxidasae-halide system. It was also found that rifamycins in combination with clarithromycin could have a good bactericidal effect in the PAM-model of the infection. Clinical evaluations suggested that defect in local pulmonary defense, such as healed pulmonary tuberculous lesions, pneumoconiosis, and COPD was more important predisposing factor than defect in systemic defense in the development of PMAC. Most patients having PMAC without predisposing factors are elderly women, the reason of which is the most important question to be answered in the future studies.
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PMID:[Basic and clinical studies on pathogenesis of pulmonary Mycobacterium avium complex disease]. 938 57


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