Increased soluble tumor necrosis factor receptor expression and release by human immunodeficiency virus type 1 infection.
High levels of circulating soluble tumor necrosis factor receptors (sTNF-R) are associated with HIV-1 infection and disease. To understand better this association, we have investigated p55 and p75 TNF-R expression on peripheral blood mononuclear cell (PBMC) subsets and in the promonocytic cell line U937, with or without HIV infection. Using flow cytometry and monoclonal antibodies both to sTNF-R and to PBMC subsets, TNF-R were found to be expressed mostly by monocytes and in decreasing amounts and intensity in the following order: CD14+ cells > CD8+ cells > CD4+ cells. Expression of TNF-R was higher on cells obtained from HIV-infected than from noninfected subjects, and expression of p75 sTNF-R was much higher than that of p55 sTNF-R. Studying the U937 cells revealed that over 80% of the cells expressed both sTNF-R, but with greater fluorescence intensity in the HIV-1 chronically infected cells (U-937-IIIB). Treatment of the cells with PMA caused an accelerated release into the medium of both sTNF-R, with a sharp decline in their cell surface expression. Basal levels of mRNA transcripts for p75 TNF-R were higher in the U-937-IIIB cells than in the uninfected cells, but p55 TNF-R mRNA was expressed only in the HIV-1-infected cells. These findings show that HIV-1 infection is accompanied by predominant elevation of p75 TNF-R surface expression on monocytes and CD8+ lymphocytes, and results in both increased message and expression of these receptors in monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
R. Ben-Ari Institute of Clinical Immunology, Kaplan Hospital, Hebrew University Medical School, Rehovot, Israel.
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A
Kalinkovich
R
R
Geleziunas
O
O
Kemper
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D
Belenki
D
D
Wallach
M A
MA
Wainberg
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Bentwich
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology*; D002460:Cell Line; D015497:HIV-1; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D018655:Lymphocyte Count; D009000:Monocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis* / Q000378:metabolism; D012995:Solubility; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014779:Virus Replication / Q000187:drug effects
D015415:Biomarkers; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate