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)

Profiles of generation and characteristic of splenic macrophages (M phi s), which suppress the ConA mitogenic response of splenic T cells, induced in mice during the course of Mycobacterium avium complex infections were investigated. In MAC-infected mice, reduction of ConA mitogenesis of spleen cells (SPCs) was seen after week 2 and the reduced state thereafter durated as long as at least for 8 weeks. Splenic M phi s with a potent suppressive activity against SPC mitogenesis were transiently induced around 2 weeks after infection. Splenic M phi s of BALB/c (MAC-susceptible) mice had similar but somewhat weaker suppressor activity, as compared to those of CBA/JN (MAC-resistant) mice. The suppressor activity of BALB/c M phi s durated much longer than did CBA/JN M phi s. MAC-induced splenic M phi s were markedly elevated in chemiluminescence and this coincided with increase in immunosuppressive activity. These M phi s inhibited the generation of IL-2-reactive T cell populations in response to ConA-signals, without showing any inhibitory effect against IL-2 producing ability of target T cells. Because immunosuppressive M phi s having the same characteristics were also induced in BALB/c athymic nude mice, thereby indicating that mature T cells are not prerequisite for induction of the present suppressor M phi s in MAC-infected host mice. Prostaglandins (PGs), nitric oxide radical (NO.) and free long chain fatty acids are thought to play certain role in the expression of suppressor action of MAC-induced M phi s, because of the following reasons.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Immunosuppressive macrophages induced in Mycobacterium avium complex infection induced in mice]. 154 8

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

Lymphocyte functions of the peripheral blood in the patients infected with MAC (MAC-pts) were evaluated comparatively with age-matched normal controls by using flow cytometry. The results obtained were as follows: 1) In normal controls, the number of total lymphocytes and the proportion and number of T lymphocyte subsets significantly decreased with age. The proportion of natural killer lymphocytes significantly increased in elder controls. 2) In MAC-pts, the number of total lymphocytes and T lymphocyte subsets were significantly lower and the proportion of natural killer lymphocytes were higher respectively than normal controls. 3) The lymphocyte proliferation induced by PPD-S stimulation in vitro in MAC-pts was significantly lower than the normal controls in both age groups of 50-69 and 70-89 years old. 4) The lymphocyte proliferation induced by PPD-S stimulation in MAC-pts was increased slightly by adding recombinant IL-2 and significantly higher by depletion of monocytes. By combination of both treatments, it recovered to the level of normal controls. From these results, we suggested that the decline of lymphocyte proliferation induced by PPD-S stimulation in MAC-pts was due to the decrease of IL-2 production by antigen committed lymphocytes and suppression by monocytes. 5) Lymphocyte proliferation induced by PHA stimulation in vitro was also significantly depressed in MAC-pts as compared with normal controls.
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PMID:[Clinico-immunological study of the patients infected with Mycobacterium avium complex (MAC)]. 154 10

Flow cytometry (FC) and fluorescent in situ hybridization (FISH) were used to detect in vivo induced IL-1 alpha (a) messenger RNA. Spleen cells and thioglycollate-induced peritoneal exudate cells (PEC) were harvested from Balb/C mice three hours after intraperitoneal injection of 20 micrograms LPS. Cells from each population were phenotyped for MAC or IAd, fixed in 4% paraformaldehyde and then permeabilized with 70% ETOH. RNA-RNA FISH was performed by incubating suspended cells at 37 degrees C for 17 hours with biotinylated sense IL-1a, antisense IL-1a or antisense IL-2 probes in 50% formamide. Hybridized cells were washed in 2X SSC, treated with RNAse, stained with avidin conjugated to fluorescein (FITC) or allophycocyanin (APC) and analyzed immediately by FC. Initially, avidin-FITC was used to detect hybridized probe. Dual fluorescent FC analysis of IL-1a mRNA expression in LPS stimulated IAd+ cells showed an increase in mean fluorescent intensity (MFI) of 51 log channels (0.25 logs) when compared to unstimulated cells. Additionally, induction of specific IL-1a mRNA expression in cells from LPS treated animals was illustrated by increases in percent positive cells (24%) and in equivalent soluble fluorescein molecules (ESFM) bound (47%) when compared to cells from vehicle treated mice. Unhybridized cells and cells hybridized with control antisense IL-2 probe did not exhibit increases in MFI or ESFM. In subsequent experiments on MAC+ PEC, the use of avidin-APC to detect bound probe resulted in a greater separation between the FISH signals of antisense IL-1a and control sense probe (121 log channels, 0.6 logs) than that seen with FITC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection of in vivo-induced IL-1 mRNA in murine cells by flow cytometry (FC) and fluorescent in situ hybridization (FISH). 157 48

The requirements for activation of anti-mycobacterial and anti-listerial activity of human monocytes were investigated. Human monocytes could be activated to display enhanced anti-mycobacterial activity by a 24-h treatment with lipopolysaccharide. The mediator induced by this treatment was identified as being tumour necrosis factor-alpha (TNF-alpha). Addition of recombinant TNF-alpha (rTNF-alpha) to the cultures of human monocytes for 24 h yielded comparable results (minimal dose required for induction of anti-mycobacterial activity, 10 U ml). Addition of anti-TNF-alpha antibody completely abrogated the effect. A similar treatment protocol failed to activate enhanced anti-listerial activity. To trigger anti-listerial activity, sequential treatment of human monocytes with rTNF-alpha and IL-2 was required. Treatment of monocytes with 10 U ml rTNF-alpha for 24 h followed by incubation in the presence of 200 U/ml of IL-2 for an additional 24 h yielded a reduction of listerial growth which was moderate but statistically significant (P less than 0.001). The activation of monocytes observed with rTNF-alpha/IL-2 treatment was (i) dependent on both cytokines; (ii) sequence dependent (i.e. when IL-2 was added prior to rTNF-alpha, no effect was observed); and (iii) absent in cells treated with one cytokine only. Enhancement of anti-listerial activity by sequential use of cytokines was not accompanied by an increase in oxidative burst, which indicated that oxidative mechanisms were not the reason for the observed Listeria monocytogenes growth restriction. Further support for this hypothesis was obtained after interferon-gamma treatment of human monocytes which led to an augmented PMA-inducible release of active oxygen radicals, but was not paralleled by growth restriction of L. monocytogenes. Our results indicate that TNF-alpha plays a crucial role in the activation of monocytes for growth restriction of intracellular microbes. Activation of human monocytes to restrict the growth of the facultative intracellular bacteria Mycobacterium avium intracellulare and L. monocytogenes, however, follows different patterns, the initial trigger in both cases being provided by TNF-alpha-induced signals.
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PMID:Induction of anti-mycobacterial and anti-listerial activity of human monocytes requires different activation signals. 164 23

Host defense mechanisms against Mycobacterium avium complex (MAC) are poorly understood. Recent evidence suggests the role of NK cells in the host defense against some intracellular pathogens. We investigated whether NK cells play a role in MAC infection. IL-2-activated human NK cells were incubated with human monocyte-derived macrophages either before or after infection with MAC. Macrophages were lysed 3 and 5 days after infection for quantitation of viable intracellular organisms. Although no killing was observed by nonstimulated macrophages, exposure to IL-2-treated NK cells for 24 h before infection induced macrophage to kill 70 +/- 8% of intracellular MAC by 3 days, and 81% +/- 4% in 5 days (p less than 0.01 for both compared with control). Killing was not blocked by incubation with anti-TNF antibody (Ab) or anti-IFN-gamma Ab. Similarly, incubation of macrophages for 24 h with supernatant obtained from IL-2 activated NK cells was associated with 74 +/- 4% killing of intracellular MAC in 3 days and 81 +/- 6% in 5 days (p less than 0.01 for both compared with control). However, the supernatant-mediated activation was partially blocked by anti-TNF Ab (46 +/- 6%; p less than 0.05) but not by anti-IFN gamma Ab. When infected macrophages were incubated with NK cells 24 h after infection for 48 h, they killed 54 +/- 3% of intracellular M. avium in 3 days and 73 +/- 5% in 5 days (p less than 0.02 for both compared with control). This effect was also not blocked by either anti-TNF or anti-IFN gamma Ab. These results suggest that activated NK cells may have an important role in the intracellular killing of MAC and that the NK-mediated activation of macrophages is in part mediated by TNF.
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PMID:Natural killer cell-dependent mycobacteriostatic and mycobactericidal activity in human macrophages. 189 1

Cytogenetic, immunologic and DNA studies were performed on a patient with the T-cell type of chronic lymphocytic leukaemia. Standard G-banding karyotype analysis revealed clonal chromosome abnormalities with the karyotype 42-44,XY,-11,-12,-13,-16,-21,-22,i(8q),inv(14) (q11q32), t(15;?)(p11;?), +4-6mar/43-44,X,t(Y;14)(p11;q11),-11,-12, -13,-21,-22,i(6p),i(8q),inv(14)(q11q32),t(15;?)(q11;?), +1-3mar. MAC (morphology, antibody, chromosomes) methodology, which allows the immunophenotyping of mitotic cells, showed that the chromosome abnormalities were restricted to CD4-positive helper/inducer T lymphocytes and that CD8 suppressor/cytotoxic T cells and B lymphocytes possessed a normal karyotype. The results also indicate that the proportion of abnormal metaphases and the overall mitotic activity after 3.5 days of stimulation in vitro were highest when PHA and TPA were used as mitogens. When the culture period in the presence of PHA + IL-2 was extended, the proportion of the abnormal cell population decreased in direct relation to the length of the culture period, ranging from 100% at 3.5 d to 0% at 31 d after stimulation. Southern blotting analysis revealed rearrangements of both the immunoglobulin heavy chain gene and the beta T-cell receptor gene.
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PMID:Chromosomal abnormality limited to T4 lymphocytes in a patient with T-cell chronic lymphocytic leukaemia. 197 8

The profile of generation and characteristics of immunosuppressive macrophages (M phi s), which suppress the ConA-mitogenic response of spleen cells (SPCs), in host CBA/JN mice during the course of Mycobacterium avium complex (MAC) and M. tuberculosis (MT) infections were investigated. In both infections, a marked reduction in ConA mitogenic response of splenic T cells was seen around 2 weeks after infection, and this was accompanied by generation of potent immunosuppressive M phi s in the SPCs of infected mice. The suppressive activity was much stronger in MT-infected mice than in MAC-infected ones. In both infections, the large part of the suppressive M phi s exhibited suppressor activity that depended on the arachidonic acid cascade, particularly mediated by prostaglandins (PGs), and the remainder showed the suppressor action independent from PGs. The unique finding of this study is that the generation of IL-2 reactive T cell populations in SPCs in response to ConA signal was markedly inhibited by the MAC- and MT-induced immunosuppressive M phi s, whereas the suppressive M phi s failed to reduce the IL-2-producing ability of splenic T cells. In any case, the present results indicate a close similarity in immunosuppressive M phi s induced by MAC and MT infections.
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PMID:Characteristics of immunosuppressive macrophages induced in host spleen cells by Mycobacterium avium complex and Mycobacterium tuberculosis infections in mice. 216 97

The profile of generation and characteristics of splenic macrophages (M phi s) which suppress the concanavalin A (Con A) mitogenic response of splenic T cells (designated as 'immunosuppressive M phi s') in host CBA/JN mice during the course of Mycobacterium avium complex (MAC) infection were investigated. In MAC-infected mice, reductions in some cellular functions of host splenic T cells, such as the Con A mitogenic response and mixed leucocyte reaction, were seen around 2 weeks after challenge of organisms, and this was accompanied by appearance of immunosuppressive M phi s in spleen cells. In this case, increase in immunosuppressive M phi activity was seen in terms of both activity per spleen and activity per individual M phi. In this phase of the infection, MAC-induced splenic M phi s showed a markedly increased ability to produce reactive oxygen radicals in response to phorbol myristate acetate. Thus, the expression of suppressor activity of MAC-induced M phi s seems to be closely linked to their activated state. A large proportion of the immunosuppressive M phi s exhibited suppressor activity dependent on prostaglandins and membrane functions related to microfilaments. It was also found that the generation of IL-2-reactive T cell populations in response to Con A was markedly inhibited by MAC-induced splenic M phi s, whereas they caused no significant reduction in the IL-2-producing ability of normal spleen cells.
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PMID:Characteristics of immunosuppressive macrophages induced in spleen cells by Mycobacterium avium complex infections in mice. 238 Jun 90

We have previously described a variant murine CTL clone that in contrast to all other clones tested, exhibited a novel capacity to produce IFN-gamma in response to IL-2. This alternative pathway of IFN-gamma induction differed from the conventional TCR complex-mediated pathway in that it was independent of elevated intracellular Ca2+ and insensitive to cyclosporine A. We report here the presence of an analogous pathway in the majority of T lymphocyte clones tested, when these clones are stimulated with IL-2 in the presence of syngeneic or third-party splenocytes. The accessory function of splenocytes in this alternative pathway is mediated by the MAC-1+ subpopulation and apparently involves cell-cell contact. However, the structure with which the MAC-1 antibody reacts probably is not involved directly. No involvement of Ag or the TCR for Ag could be demonstrated in this alternative pathway of lymphokine induction. The array of lymphokines induced by this alternative pathway is only a subset of those induced by antigenic stimulation. Finally, as with the previously described variant clone, IL-2-mediated induction of IFN-gamma production by the normal T lymphocyte clones is independent of normal extracellular Ca2+ levels and insensitive to cyclosporine A. Thus, this alternative pathway of lymphokine induction apparently constitutes a distinct signaling pathway in cloned T lymphocytes.
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PMID:An alternative pathway of induction of lymphokine production by T lymphocyte clones. 249 82


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