HIV-1-infected myelomonocytic cells are resistant to Fas-mediated apoptosis: effect of tumor necrosis factor-alpha on their Fas expression and apoptosis.
To get insight into the involvement of tumor necrosis factor-alpha (TNF-alpha) and Fas (CD95) ligand in apoptosis (programmed cell death) of monocyte/macrophages in HIV-1-infected individuals, various T cell and myelomonocytic cell lines, including the HIV-1-infected clones OM-10.1 and U1 cells, were cultured in the presence of either TNF-alpha alone, anti-Fas agonist monoclonal antibody (Fas-mAb) alone, or their combinations. TNF-alpha moderately decreased the viability of myelomonocytic cell lines in a dose-dependent fashion (1-100 ng/ml). Unlike HIV-1-infected T cell lines, the viability of OM-10.1 and U1 cells was not affected by the treatment with Fas-mAb alone at concentrations up to 1,000 ng/ml. However, the viability of OM-10.1 cells further decreased with increasing concentrations of Fas-mAb when exposed simultaneously to TNF-alpha, suggesting that TNF-alpha sensitizes the cells to Fas-mAb-induced cell death. FACScan analysis and DNA gel electrophoresis revealed that the cell death was due to apoptosis. Such an effect of Fas-mAb was not identified in U1 cells. TNF-alpha but not Fas-mAb activated latent HIV-1 in OM-10.1 and U1 cells. Although all myelomonocytic cell lines expressed Fas on their cell surface, TNF-alpha significantly up-regulated the expression of Fas in only OM-10.1 cells. These results indicate that, unlike T cells, HIV-1-infected myelomonocytic cells are generally resistant to the Fas-mediated apoptosis. However, they would become sensitive to the apoptosis if the expression of Fas could be up-regulated by TNF-alpha or other factors.
Okamoto
M
M
Division of Human Retroviruses, Faculty of Medicine, Kagoshima University, Japan.
Makino
M
M
Kitajima
I
I
Maruyama
I
I
Baba
M
M
D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis; D002460:Cell Line; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D009000:Monocytes / Q000821:virology; D013601:T-Lymphocytes / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation; D014775:Virus Activation; D019014:fas Receptor / Q000032:analysis / Q000502:physiology*
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor