DESENSITIZATION OF FORMYL PEPTIDE RECEPTORS IS ABOLISHED IN CALCIUM IONOPHORE-PRIMED NEUTROPHILS - AN ASSOCIATION OF THE LIGAND-RECEPTOR COMPLEX TO THE CYTOSKELETON IS NOT REQUIRED FOR A RAPID TERMINATION OF THE NADPH-OXIDASE RESPONSE

Binding of ligands to N-formyl peptide chemoattractant receptors expos ed on human neutrophils generates signals in the cells that induce an activation of the superoxide anion producing NADPH-oxidase. Ligand bin ding is followed by a rapid association of the ligand-receptor complex with the cytoskeleton, a process leading to desensitization of the ce lls with respect to NADPH-oxidase activation, We show that neutrophils that have experienced an intracellular calcium rise obtained through interaction with the calcium-specific ionophore ionomycin are ''primed '' with respect to the FMLP-induced production of superoxide anions. M obilization of FMLP receptors from intracellular pools is one well-kno wn mechanism behind the primed response, Based on our finding that ion omycin-treated neutrophils could not be desensitized, we suggest that the lack of association between the ligand-receptor complex and the cy toskeleton is an additional priming mechanism, Since in vivo-exudated neutrophils, which also had mobilized intracellular organelles, could be desensitized, we suggest that the abolished desensitization in iono mycin-treated neutrophils is not due to an inability of newly recruite d receptors to couple to the cytoskeleton, We show that a rapid termin ation of FMLP-induced superoxide anion production is obtained in both desensitizable and nondesensitizable neutrophils, suggesting that the desensitization phenomenon is of limited importance in the oxidase ter mination process.