CHARACTERIZATION OF A COMPLEMENT-FRAGMENT-C5A-STIMULATED CALCIUM-INFLUX MECHANISM IN U937 MONOCYTIC CELLS

The mechanism by which complement fragment C5a elevates intracellular Ca2+ ([Ca2+]i) levels in two cell types, a monocytic cell line, U937, and neutrophils, has been investigated by the use of fluorometric and radiometric techniques. In U937 cells the influx of extracellular Ca2 can be distinguished from the release of intracellular Ca2+ stores in terms of dose-responsiveness to C5a and sensitivity to pertussis-toxi n poisoning. This suggests that the mechanism of Ca2+ influx in these cells is at least partially independent of both the production of inos itol phosphates and elevation of internal Ca2+ concentration. The C5a- stimulated influx of Ca-45(2+) into U937 cells is inhibited by a serie s of metal ions (Zn2+ > Co2+ > Mn2+ > Sr2+ congruent-to Ni2+ > La3+). The stimulated influx of Ca2+ into neutrophils is inhibited differentl y (Ni2 much greater than Co2+ > Zn2+ congreunt-to La3+ > Mn2+ congruen t-to Sr2+), is less sensitive to C5a and both the influx of extracellu lar Ca2+ and the release of intracellular stores are equally sensitive to pertussis toxin treatment. Taken together these results indicate t hat [Ca2+]i is controlled in U937 monocytes by mechanisms distinct fro m those which appear to operate in other myeloid cells, such as neutro phils, stimulated with C5a and formylpeptide.