REGULATION OF NEUTROPHIL O-2(-) PRODUCTION BY NEUTROPHIL-ENDOTHELIAL CELL-INTERACTION VIA CD11B - ITS MODULATION BY TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) AND LIPOPOLYSACCHARIDE (LPS)

Polymorphonuclear leukocyte-endothelial cell (PMN-EC) adhesion and the O-2(-) production by subsequently triggered polymorphonuclear leukocy tes (PMN) must be involved in the development of multiple organ failur e at septic inflammatory sites. In this study, the adhesion and O-2(-) production of PMN treated with LPS and serum, were markedly enhanced on the EC monolayer by treatment with TNF-alpha or LPS. However, in th e intact EC monolayer, neither adhesion nor O-2(-) production was incr eased. Monoclonal antibodies (mAb) against CD11b, and ICAM-1 inhibited PMN-EC adhesion. All antibodies except for anti-CD11b mAb had no effe ct on O-2(-) production by adhered PMN. Anti-CD11b mAb stimulated O-2( -) production in a PMN cell suspension. The pertussis toxin, an inhibi tor of some G-proteins, inhibited this reaction. These findings indica te that the adhesion mediated by CD11b provides the signal for O-2(-) production by PMN. This O-2(-) production may involve a signal transdu ction mechanism mediated by pertussis toxin-sensitive G-proteins.