Chemotactic factor receptor activation transiently impairs the Ca2+ signaling capacity of beta 2 integrins on human neutrophils.
Neutrophil motility involves a delicate interplay between intracellular signals elicited by adhesion and chemotactic factor receptors. To explore certain aspects of these complex receptor interactions in neutrophils, we studied how engagement of the chemotactic receptor for N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe) and the beta 2 integrins affect the Ca2+ signaling properties of each other. Specific antibody engagement of the beta 2 integrins on suspended neutrophils generated both an intracellular mobilization and an influx of Ca2+, effects which could be temporarily impaired by preengaging the fMet-Leu-Phe receptors on the cells. In contrast to these findings, preengagement of the beta 2 integrins on suspended neutrophils affected neither a subsequent fMet-Leu-Phe-induced mobilization of Ca2+ nor an influx 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 preactivation 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 intracellular stores.
Eierman
D
D
Liposome Company, Princeton, New Jersey 08540.
Hellberg
C
C
Sjölander
A
A
Andersson
T
T
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018821:CD18 Antigens; D002118:Calcium / Q000097:blood*; D002448:Cell Adhesion; D003600:Cytosol / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D016257:Fura-2; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000502:physiology*; D007700:Kinetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000187:drug effects / Q000502:physiology*; D018000:Receptors, Peptide / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction; D013997:Time Factors
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D016023:Integrins; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D004533:Egtazic Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002118:Calcium; D016257:Fura-2