Increased soluble tumor necrosis factor receptor expression and release by human immunodeficiency virus type 1 infection

J Interferon Cytokine Res. 1995 Sep;15(9):749-57. doi: 10.1089/jir.1995.15.749.

Abstract

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)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / blood*
  • Biomarkers / blood
  • CD8-Positive T-Lymphocytes / pathology*
  • Cell Line
  • HIV-1*
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Count
  • Monocytes / metabolism
  • RNA, Messenger / biosynthesis
  • Receptors, Tumor Necrosis Factor / biosynthesis*
  • Receptors, Tumor Necrosis Factor / metabolism
  • Solubility
  • Tetradecanoylphorbol Acetate / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Virus Replication / drug effects

Substances

  • Biomarkers
  • RNA, Messenger
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Tetradecanoylphorbol Acetate