CHEMOTACTIC FACTOR-RECEPTOR ACTIVATION TRANSIENTLY IMPAIRS THE CA2+ SIGNALING CAPACITY OF BETA(2) INTEGRINS ON HUMAN NEUTROPHILS

Neutrophil motility involves a delicate interplay between intracellula r signals elicited by adhesion and chemotactic factor receptors. To ex plore certain aspects of these complex receptor interactions in neutro phils, we studied how engagement of the chemotactic receptor for N-for myl-L-methionyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe) and the beta(2 ) integrins affect the Ca2+ signaling properties of each other. Specif ic antibody engagement of the beta(2) integrins on suspended neutrophi ls generated both an intracellular mobilization and an influx of Ca2+, effects which could be temporarily impaired by preengaging the fMet-L eu-Phe receptors on the cells. In contrast to these findings, preengag ement of the beta(2) integrins on suspended neutrophils affected neith er a subsequent fMet-Leu-Phe-induced mobilization of Ca2+ nor an influ x of Ca2+ from outside the cell. We also found that fMet-Leu-Phe could mobilize intracellular Ca2+ after a premobilization of Ca2+ via beta( 2) integrins, despite the fact that both receptors mobilize Ca2+ from thapsigargin-sensitive intracellular stores. The findings that preacti vation of beta(2) integrins did not affect the ability of fMet-Leu-Phe to induce an intracellular Ca2+ signal, whereas preactivation of fMet -Leu-Phe receptors transiently impaired the Ca2+ signaling ability of beta(2) integrins, suggest that the fMet-Leu-Phe-induced reduction is due to an interaction upstream of the release of Ca2+ from intracellul ar stores. (c) 1994 Academic Press, Inc.