抄録
Both monocyte chemotactic and activating factor (MCAF) and N-formyl-methionyl-leucyl-phenylalanine (FMLP) stimulated an increase in cytoplasmic free Ca2+ ( [Ca2+] i) and changes in intracellular pH (pHi) in human monocytes in parallel at lower concentrations, and stimulated superoxide (O-2) release and changes in transmembrane potential in parallel at higher concentrations. The changes in pHi were characterized by initial rapid acidification followed by sustained alkalinization, and the changes in transmembrane potential were characterized by initial depolarization followed by partial repolarization. The time-courses of all responses stimulated by MCAF and FMLP were similar to each other, although the magnitude of all responses was less in MCAF-stimulated cells. MCAF by itself was a very weak stimulus for inducing O-2 release. However, MCAF primed monocytes and enhanced O-2 release stimulated by FMLP. The priming effect of MCAF was maximal within 5 min of preincubation, and the doseresponse curves for priming were identical to those for triggering of an increase in [Ca2+] i and intracellular acidification. Intracellular acidification was induced at lower concentration than O-2 release by MCAF stimulated monocytes. MCAF further potentiated FMLP-induced O-2 release in tumor necrosis factor (TNF) -, granulocyte-macrophage colony-stimulating factor (GM-CSF) -or IL-3-primed monocytes.
These findings suggest that MCAF, alone or in concert with other cytokines, primes monocytes for enhanced release of O-2, and that stimulus induced acidification is closely associated with an increase in [Ca2+] i, but not O-2 release.
