Priming of the respiratory burst of human neutrophils by the diadenosine polyphosphates, AP4A and AP3A: role of intracellular calcium.
The diadenosine polyphosphates, Ap3A and Ap4A, prime the respiratory burst of human neutrophils after stimulation with fMet-Leu-Phe. Maximal priming of oxidase activity occurred at 600-800 microM Ap3A and Ap4A, compared with maximal priming observed at 200 microM 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 microM Ap3A and Ap4A and < 0.1 microM 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+.
Department of Biochemistry, University of Liverpool, U.K.
L
L
Gasmi
A G
AG
McLennan
S W
SW
Edwards
D000255:Adenosine Triphosphate / Q000494:pharmacology; D002118:Calcium / Q000097:blood*; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008163:Luminescent Measurements; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D013481:Superoxides / Q000097:blood*
D015226:Dinucleoside Phosphates; D013481:Superoxides; C020733:diadenosine tetraphosphate; C011440:diadenosine triphosphate; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000255:Adenosine Triphosphate; D002118:Calcium