The secretion of tumor necrosis factor (TNF) by human peripheral blood mononuclear cells was suppressed by either whole human plasma α-globulins or purified α1-acid-glycoprotein, α1-antitrypsin and α2-macroglobulin in a concentration-dependent manner. α1-Antitrypsin was found to be the most suppressive of the purified proteins tested and completely blocked TNF release at concentrations above 1.25 mg/ml. Both α1-acid glycoprotein and α1-antitrypsin blocked TNF secretion by leukocytes which were simultaneously stimulated with either recombinant human interferon-γ (IFN-γ) or lipopolysaccharide (LPS). IFN-γ and LPS-activated cells were also susceptible to suppression mediated by these two α-globulins and the inhibition produced by 5 mg/ml α1-antitrypsin was greater than that caused by either 1 μM prostaglandin E2 or 10 ng/ml transforming growth factor-β1. The level of TNF mRNA in TNF-secreting and α-globulin-suppressed cells was examined and found to be to equal in both groups. The suppressive effect of whole α-globulins was confined to the inhibition of TNF secretion and these plasma proteins had no effect on the cytolytic activity of the recombinant cytokine as measured on murine L-929 target cells. Thus the α-globulins, which are a major fraction of the circulating plasma proteins, may function in TNF homeostasis by controlling TNF secretion without inhibiting the biological activity of the released cytokine.
|Original language||English (US)|
|Number of pages||4|
|Journal||European Journal of Immunology|
|Publication status||Published - 1989|
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