Tumor Necrosis Factor-a and FMLP Receptors Are Functionally Linked During FMLP-Stimulated Activation

Human peripheral blood neutrophils (PMN) plated onto fibrinogen and activated with FMLP release HtOt and lactoferrin, a specific granule component, with parallel kinetics. Although tumor necrosis factor-a (TNFa) only primes PMN in suspension, it is a potent agonist of adherent PMN. Activation of adherent PMN by FMLP (lo-’ mol/L) stimulated detectable release of TNFa within 45 minutes of stimulation, with maximal release (45.5 pg/106 cells) detected by 90 minutes. TNFa release paralleled the release of both lactoferrin and HZ02. To determine if TNFa plays a role in H202 and lactoferrin release, we investigated the effect of anti-TNFa antibodies on FMLP-stimulated activation of adherent PMN. A neutralizing rabbit anti-TNFa antibody inhibited both HZ02 and lactoferrin release stimulated by FMLP, whereas rabbit IgG, anti-HLA-A.B.C. anti-CD14, and anti-interleukin-8 antibodies were without effect. The simultaneous addition of TNFa (1.000 U/mL) with anti-TNFa antibody reversed the inhibition seen with anti-TNFa alone. Furthermore, treat-