THE LOSS OF RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR AND RECOMBINANT HUMAN TNF-ALPHA PRIMING EFFECTS ON THE SUPEROXIDE-GENERATING RESPONSE IN EXUDATED NEUTROPHILS IS ASSOCIATED WITH A DECREASE IN THEIR RECEPTOR AFFINITIES

Several cytokines are known to enhance FMLP-stimulated superoxide gene ration in human circulating blood neutrophils through binding to their specific receptors, a process referred to as the priming effect, The priming effects produced by recombinant human granulocyte CSF (rhGCSF) and TNF-alpha (rhTNF-alpha) on FMLP-stimulated superoxide production in human and rabbit blood neutrophils were compared with their effects in their respective tissue neutrophils, i.e., human salivary and rabb it peritoneal neutrophils, The receptor binding characteristics of rhG CSF and rhTNF-alpha were also compared between the two types of neutro phils, Both rhGCSF and rhTNF-alpha produced dose-dependent priming eff ects on FMLP-stimulated superoxide production in human blood neutrophi ls, whereas they failed to produce any priming effects in human saliva ry neutrophils. Similar results were obtained for the priming effects by rhGCSF in rabbit blood and peritoneal neutrophils, A decrease in re ceptor binding affinity, but not in receptor density, in tissue neutro phils was demonstrated by analyzing the binding of [I-125]rhGCSF and [ I-125]rhTNF-alpha. These findings suggest that tissue neutrophils are less responsive to rhGCSF and rhTNF-alpha in the modulation of FMLP-st imulated superoxide generation, This is due at least in part to the lo wer affinities of GCSF and TNF-alpha to their receptors in tissue neut rophils, This marked difference in priming effects by cytokines betwee n blood and tissue neutrophils may represent an early step in the defe nsive responses against invading microorganisms or Ag.