Association of circulating receptor Fc gamma RIII-positive monocytes in AIDS patients with elevated levels of transforming growth factor-beta (original) (raw)
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HIV-1 gp160 Induces Transforming Growth Factor-β Production in Human PBMC
Clinical Immunology and Immunopathology, 1996
The mechanisms by which HIV infection results in Transforming growth factor-b (TGF-b) is a multiinduction of TGF-b secretion is however unknown. The functional cytokine secreted by many mononuclear HIV envelope glycoprotein gp160, which is expressed cells in peripheral blood (PBMC) and has diverse efon the surface of HIV and of HIV-infected cells, interfects on cellular and humoral immunity. Increased acts with the CD4 receptor of CD4-bearing T cells and TGF-b mRNA expression has been reported in PBMC macrophages with high affinity and has been shown of HIV-infected patients, but the mechanism by which to induce a variety of cytokines from T cells and/or HIV induces TGF-b secretion is unknown. In this macrophages (9-11). We have previously demonstudy, we observed that HIV gp160 could induce sigstrated that gp120/gp160 could induce IL-6/GM-CSF/ nificant TGF-b secretion and TGF-b mRNA expression IL-3 mRNA expression and cytokine secretion in pein PBMC from HIV-seronegative healthy donors. The ripheral blood mononuclear cells (PBMC), CD4 / T cell cellular source of TGF-b was attributed to non-T cells, clones, and cord blood T cells (12, 13). Other groups presumably monocytes. Specificity of secreted TGF-b have shown that gp120 can induce IL-1b and TNF-a was confirmed by the addition of anti-TGF-b mAb in macrophages as well (14). In the present study, we which abrogated the proliferative response of CCL-64 have investigated the influence of the highly purified cells by gp160-treated culture supernatants. Soluble native gp160 in inducing TGF-b production. Here, we CD4 blocked the gp160-induced TGF-b production, demonstrate that in vitro exposure of normal PBMC to suggesting that CD4-gp160 interaction is required to induce TGF-b production. Our results suggest that gp160 results in the induction of TGF-b mRNA expres-HIV-1 gp160 may contribute to the immune defects in sion and secretion of bioactive molecules. Soluble CD4 HIV infection by inducing TGF-b secretion. ᭧ 1996 blocked the gp160-induced TGF-b production, sug-Academic Press, Inc.
HIV-1 gp160 Induces Transforming Growth Factor-� Production in Human PBMC
Clinical Immunology and Immunopathology, 1996
The mechanisms by which HIV infection results in Transforming growth factor-b (TGF-b) is a multiinduction of TGF-b secretion is however unknown. The functional cytokine secreted by many mononuclear HIV envelope glycoprotein gp160, which is expressed cells in peripheral blood (PBMC) and has diverse efon the surface of HIV and of HIV-infected cells, interfects on cellular and humoral immunity. Increased acts with the CD4 receptor of CD4-bearing T cells and TGF-b mRNA expression has been reported in PBMC macrophages with high affinity and has been shown of HIV-infected patients, but the mechanism by which to induce a variety of cytokines from T cells and/or HIV induces TGF-b secretion is unknown. In this macrophages (9-11). We have previously demonstudy, we observed that HIV gp160 could induce sigstrated that gp120/gp160 could induce IL-6/GM-CSF/ nificant TGF-b secretion and TGF-b mRNA expression IL-3 mRNA expression and cytokine secretion in pein PBMC from HIV-seronegative healthy donors. The ripheral blood mononuclear cells (PBMC), CD4 / T cell cellular source of TGF-b was attributed to non-T cells, clones, and cord blood T cells (12, 13). Other groups presumably monocytes. Specificity of secreted TGF-b have shown that gp120 can induce IL-1b and TNF-a was confirmed by the addition of anti-TGF-b mAb in macrophages as well (14). In the present study, we which abrogated the proliferative response of CCL-64 have investigated the influence of the highly purified cells by gp160-treated culture supernatants. Soluble native gp160 in inducing TGF-b production. Here, we CD4 blocked the gp160-induced TGF-b production, demonstrate that in vitro exposure of normal PBMC to suggesting that CD4-gp160 interaction is required to induce TGF-b production. Our results suggest that gp160 results in the induction of TGF-b mRNA expres-HIV-1 gp160 may contribute to the immune defects in sion and secretion of bioactive molecules. Soluble CD4 HIV infection by inducing TGF-b secretion. ᭧ 1996 blocked the gp160-induced TGF-b production, sug-Academic Press, Inc.
Clinical & Experimental Immunology
IgA is the predominant immunoglobulin in human secretions and the second most important immunoglobulin in the circulation on a quantitative basis. The clearance of IgA is dependent on the function of at least three types of receptors. One of these receptors recognizes the Fc portion of the IgA molecule, Fc alpha R, which has been cloned recently. Fc alpha R, also designated CD89, is found on a number of cells, including human glomerular mesangial cells, and monocytes. In this study we analysed the effect of TGF-beta 1, a cytokine with strong immunosuppressive function, on the expression of CD89 on freshly isolated monocytes. We found that TGF-beta 1 down-regulates CD89 expression on human peripheral blood monocytes in a dose-dependent fashion. Optimal down-regulation occurred at a concentration of 5 ng/ml. The down-regulation of CD89 by TGF-beta 1 is linear in time, with a mean down-regulation of 34 +/- 13% after 24 h. Also at the mRNA level, CD89 expression was down-regulated by TG...
Frontiers in Immunology, 2017
Even after attainment of sustained viral suppression following implementation of highly active antiretroviral therapy, HIV-infected persons continue to experience persistent, low-grade, systemic inflammation. Among other mechanisms, this appears to result from ongoing microbial translocation from a damaged gastrointestinal tract. This HIVrelated chronic inflammatory response is paralleled by counteracting, but only partially effective, biological anti-inflammatory processes. Paradoxically, however, this antiinflammatory response not only exacerbates immunosuppression but also predisposes for development of non-AIDS-related, non-communicable disorders. With respect to the pathogenesis of both sustained immunosuppression and the increased frequency of non-AIDS-related disorders, the anti-inflammatory/profibrotic cytokine, transforming growth factor-β1 (TGF-β1), which remains persistently elevated in both untreated and virally suppressed HIV-infected persons, may provide a common link. In this context, the current review is focused on two different, albeit related, harmful activities of TGF-β1 in HIV infection. First, on the spectrum of anti-inflammatory/immunosuppressive activities of TGF-β1 and the involvement of this cytokine, derived predominantly from T regulatory cells, in driving disease progression in HIV-infected persons via both non-fibrotic and profibrotic mechanisms. Second, the possible involvement of sustained elevations in circulating and tissue TGF-β1 in the pathogenesis of non-AIDS-defining cardiovascular, hepatic, pulmonary and renal disorders, together with a brief comment on potential TGF-β1-targeted therapeutic strategies.
1997
Human immunodeficiency virus-1 (HIV-1) Tat protein can be firming the common use of this receptor. Binding studies performed at equilibrium by using radiolabeled Tat showed released by infected cells and activates mesenchymal cells. Among these, monocytes respond to Tat by migrating into that monocytes expressed a unique class of binding site, with a kd of approximately 0.2 nmol/L. The binding of radio-tissues and releasing inflammatory mediators. In the present study, we have examined the molecular mechanism of labeled Tat to monocyte surface and the cross-linking to a protein of 150 kD was inhibited specifically by an excess of monocyte activation by Tat, showing that this viral protein signals inside the cells through the tyrosine kinase receptor cold Tat or VEGF-A. Western blot analysis with an antibody anti-VEGFR-1/Flt-1 performed on monocyte phosphopro-for vascular endothelial growth factor encoded by fms-like tyrosine kinase gene (VEGFR-1/Flt-1). Subnanomolar con-teins immunoprecipitated by an monoclonal antibody antiphosphotyrosine showed that Tat induced a rapid phosphor-centrations of Tat induced monocyte chemotaxis, which was inhibited by cell preincubation with vascular-endothelial ylation in tyrosine residue of the 150-kD VEGFR-1/Flt-1. Taken together, these results suggest that biologic activities growth factor-A (VEGF-A). This desensitisation was specific for VEGF-A, because it not was observed with FMLP. In addi-of HIV-1 Tat in human monocytes may, at least in part, be elicited by activation of VEGFR-1/Flt-1. tion, the soluble form of VEGFR-1 specifically inhibited polarization and migration induced by Tat and VEGF-A, thus con-᭧ 1997 by The American Society of Hematology. growth factor), 24 we have recently shown that the tyrosine