INTERLEUKIN-8 DOWN-REGULATES THE OXIDATIVE BURST INDUCED BY TUMOR-NECROSIS-FACTOR-ALPHA IN NEUTROPHILS ADHERENT TO FIBRONECTIN

Human neutrophils (5 x 10(4)) incubated on fibronectin precoated wells released 2.83 +/- .25 nmoles of superoxide (O-2(-)) (x +/- 1 SEM, n = 15) in response to 5.9 nM (100 ng/ml) Tumor Necrosis Factor Alpha (TN F). On the contrary, the O-2(-) production induced by interleukin-8 (I L-8) (doses ranging from 0.1 nM to 1 mu M) was comparable to that of ' 'resting'' cells (< .6 nmoles/5 x 10(4) cells). IL-8 (100 nM) did not affect the TNF-dependent O-2(-) production when added with TNF at the beginning of the assay, but reduced it by similar to 80% when added wi th TNF on neutrophils previously incubated for 1 hour on fibronectin. As compared with IL-8,N-formyl-methionyl-leucyl-phenylalanine (FMLP, 1 00 nM) failed to suppress the TNF-triggering of the oxidative burst in neutrophils plated on fibronectin. The data suggest that the interact ion of neutrophils with fibronectin uncovers the capacity of IL-8 to l imit the cell response to TNF, without affecting the response to the c ombination of FMLP and TNF. Thus, although the chemotactic factors IL- 8 and FMLP share the capacity of triggering the oxidative burst of neu trophils incubated in suspension, only IL-8 has the potential to down- regulate the responsiveness of fibronectin-adherent cells to TNF.