KILLING OF STAPHYLOCOCCUS-AUREUS BY TUMOR NECROSIS FACTOR-ALPHA-ACTIVATED NEUTROPHILS - THE ROLE OF SERUM OPSONINS, INTEGRIN RECEPTORS, RESPIRATORY BURST, AND DEGRANULATION

We have examined the effects of TNF priming on the killing of Staphylo coccus aureus by human neutrophils. In the absence of serum opsonins, neutrophils failed to kill S. aureus, and TNF priming did not induce t he cells to become bactericidal. Normal human serum, containing comple ment activity, promoted the killing of the bacteria by neutrophils. Pr etreatment of neutrophils for 30 min with TNF significantly enhanced t heir bactericidal activity. The effects of TNF on neutrophil bacterici dal activity was dependent on serum concentration and the degree of en hancement induced increased up to a concentration of 1%. The kinetics of bacterial killing showed that TNF-only enhanced the initial rate of killing, over the first 30 min. Little killing of bacteria occurred i n the presence of complement-inactivated serum, and TNF did not stimul ate this killing. These results suggest that TNF enhances the neutroph il complement-dependent killing of S. aureus. TNF increased the expres sion of CR3 (CD11b/CD18) and CR4 (P150, 95; CD11c/CD18) adhesion recep tors but not LFA-1 (CD11a/CD1 8); and mAb against the alpha-chain of e ither CR3 or CR4 but not LFA-1 prevented the enhancing effects of TNF on the neutrophil bactericidal activity.