Tumor necrosis factor induced enhancement of neutrophil chemotaxis and adhesion through mediating of phospholipase A 2 activation

Abstract

Recent studies indicate that phospholipase A 2 (PLA 2) derived lipid mediators regulate a number of neutrophil responses such as chemotaxis, adhesion and degranulation. Since tumor necrosis factor (TNF) is also a key mediator in neutrophil activation, it remains to be shown that PLA 2 is involved in the process of TNF activation. Our results shown that TNF(100 ng/ml) given in vitro for 60 min, causes an obvious enhancement of neutrophil chemotaxis towards FMLP, and increased activity of adhesion to glass beads by stimulated release of TXB 2 from PMN other than 6-keto-PGF 1a. Similer neutrophil activation responces could also be promoted by in vitro addition of arachidonic acid (1 μmol/ml) for 60 min. It was further found that PLA 2 inhibitor, 4-bromophencyl bromide (5 μmol/ml), greatly inhibite the TNF induced responces, while cycloxgenase inhibitor indomethathin (85 nmol/ml) was without effect on the activation of TNF. Those results indicated that PLA 2 activation was involved in the TNF stimulated enhancement of neutrophil chemotaxis and adhesion.