Recombinant tumor necrosis factor causes activation of human granulocytes.
We have tested the hypothesis that tumor necrosis factor (TNF), by binding to and activating granulocytes, may contribute to the pathogenesis of gram-negative sepsis and the adult respiratory distress syndrome (ARDS). Buffy coat granulocytes incubated with as little as 0.5 ng/mL of recombinant TNF (rTNF) showed a dose-related increase in nitroblue tetrazolium dye reduction, in granulocyte polarization, in superoxide anion release, and in visually apparent aggregation. Purified lipopolysaccharide (1 microgram/mL) caused polymorphonuclear (PMN) aggregation and activation that was neutralized by polymyxin B. The release of superoxide was augmented by preincubation of the PMNs with gamma-interferon. The effect of TNF was neutralized by TNF-specific murine monoclonal antibodies but not by polymyxin B. Scatchard analysis of 125I-rTNF binding to granulocytes revealed about 1,200 receptors per cell with a Kd of 4.9 X 10(-10) mol/L. These results suggest that the release of TNF by mononuclear phagocytes contributes to granulocyte activation and aggregation during inflammation.
D006023:Glycoproteins / Q000494:pharmacology*; D006098:Granulocytes / Q000187:drug effects*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha
D006023:Glycoproteins; D006131:Growth Inhibitors; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha