PRIMING OF THE RESPIRATORY BURST OF HUMAN NEUTROPHILS BY THE DIADENOSINE POLYPHOSPHATES, AP(4)A AND AP(3)A - ROLE OF INTRACELLULAR CALCIUM

The diadenosine polyphosphates, Ap(3)A and Ap(4)A,prime the respiratory burst of human neutrophils after stimulation with fMet-Leu-Phe. Maximal priming of oxidase activity occurred at 600-800 mu M Ap(3)A and Ap(4)A, compared with maximal priming observed at 200 mu M ATP. The time course of priming of the oxidase by all 3 nucleotides was very rapid, being detectable if added within 10 s of fMet-Leu-Phe. All 3 nucleotides also elicited increases in intracellular Ca2+ levels and there was a close concentration-dependency between the extent of priming and the increase in intracellular Ca2+. However, at low concentrations of nucleotides (<50 mu M Ap(3)A and Ap(4)A and < 0.1 mu M ATP) priming of the oxidase was observed without detectable increases in intracellular Ca2+. These observations indicate that diadenosine polyphosphates may be novel regulators of neutrophil function and that priming of oxidase activity may occur via mechanisms that are either dependent or independent of increases in intracellular Ca2+. (C) 1994 Academic Press, Inc.