TRIGGERING OF RESPIRATORY BURST BY TUMOR-NECROSIS-FACTOR IN NEUTROPHILS ADHERENT TO FIBRONECTIN - EVIDENCE FOR A CRUCIAL ROLE OF CD18 GLYCOPROTEINS

Human neutrophils, plated on fibronectin (FN)-coated wells, were found to release large quantities of superoxide anion (O-2(-)) in response to tumor necrosis factor alpha (TNF-alpha). The O-2(-) release was com pletely inhibited by two monoclonal antibodies (MoAbs, MHM23 and TS1/1 8) against CD18 glycoproteins. An independently derived anti-CD18 MoAb (60.3) was ineffective. These MoAbs failed to inhibit neutrophil adhe sion to FN-coated surfaces. Moreover, neutrophils incubated for 30 min on FN and then washed to remove non-adherent cells, were responsive t o TNF-alpha in the presence of anti-CD18 MoAbs MHM23 and TS1/18. Conse quently, the CD18-dependent capacitation of the respiratory burst can occur before TNF-alpha triggering. Finally, neutrophils plated on FN i n the presence of anti-CD18 MoAbs and then washed, i.e. adherent cells blocked in their surface CD18 molecules, released O-2(-) after adding TNF-alpha but only in the absence of additional anti-CD18 MoAbs. This is consistent with a TNF-alpha ability to induce rapid expression and activation of new oxidative burst-capacitating CD18 molecules. The re sults suggest that the anchorage of neutrophils to FN surfaces depends on adherence molecules apparently unrelated to CD18, probably the so- called fibronectin receptors (FNRs), whereas the capacitation of the r espiratory burst in response to TNF-alpha requires the intervention of CD18 glycoproteins, available on the membrane of ''resting'' neutroph ils or mobilized to the cell surface by TNF-alpha.