PRIMING OF NEUTROPHILS WITH TUMOR-NECROSIS-FACTOR-ALPHA MEASURED AS FC-GAMMA RECEPTOR-MEDIATED RESPIRATORY BURST CORRELATES WITH INCREASED COMPLEMENT RECEPTOR-3 MEMBRANE DENSITY

Hyperactive or primed neutrophils which damage tissue via cytokines an d membrane receptors introduction may be implicated in the pathogenesi s of inflammatory conditions. The purpose of this study was to elucida te the priming mechanism in neutrophils by assessing changes in membra ne receptors and the Fc gamma R-mediated respiratory burst, measured a s chemiluminescence. Purified neutrophilic granulocytes from healthy v olunteers were preincubated with recombinant human tumor necrosis fact or-alpha. This had a priming effect, increasing both the Fc gamma rece ptor-mediated luminol-enhanced chemiluminescence and the membrane expr ession of the C3bi receptor (CRB) (r=0.843). The membrane densities of Fc gamma RII, Fc gamma RIII, and CR1 were unaffected by tumor necrosi s factor-alpha. The mechanism of increased chemiluminescence may invol ve redistribution of the Fc gamma receptors and cooperation with upreg ulated CR3, facilitating crosslinking of the receptors. The experiment s were performed in a buffer without divalent cations, since these inc reased the background activity and abolished the priming effect of tum or necrosis factor-alpha. In conclusion, a simultaneous increase in th e Fc gamma R-mediated respiratory burst and CR3 density after priming with tumor necrosis factor-alpha indicates a cooperation between Fc ga mma R and CR3.