Regulation of oxygen radical production of human polymorphonuclear leukocytes by adenosine: the role of calcium.
In polymorphonuclear leukocytes (PMNL) adenosine is a potent inhibitor of stimulus/response coupling, as demonstrated by its adverse action on phagocytosis, degranulation and oxygen radical production. Because this nucleoside can reduce several cell functions by counteracting intracellular calcium ions (Ca2+), the present study investigates the effect of adenosine on oxygen radical production in human PMNL stimulated by N-formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe), zymosan-activated serum (ZAS) and ionophore A 23187 in a Ca(2+)-dependent manner, and stimulated by phorbol myristate acetate (PMA) and latex in a Ca(2+)-independent manner. The results demonstrate that all the Ca(2+)-dependent stimuli were concentration-dependently inhibited by adenosine. In contrast, leukocyte stimulation by the Ca(2+)-independent activator PMA was not affected by adenosine. Surprisingly, radical formation stimulated by latex beads was concentration-dependently reduced by adenosine. When intracellular Ca2+ was modified by the ionophore clamping technique or the Ca(2+)-buffering capacity of quin-2, latex-induced radical formation could be separated into two parts, one showing Ca(2+)-dependent and the other Ca(2+)-independent activation. In the presence of intracellular Ca2+, adenosine exerted a strong inhibition on the latex-induced cell activation but failed to inhibit in the Ca(2+)-depleted state. In order to elucidate a direct reduction of Ca2+ as the underlying mechanism of adenosine-mediated inhibition, intracellular Ca2+ was measured in PMNL by quin-2 fluorescence. When PMNL were activated by latex, fMet-Leu-Phe and ionophore A 23187, adenosine significantly reduced the stimulated rise in intracellular Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)
Thiel
M
M
Department of Anesthesiology, University of Munich, Klinikum Grosshadern, Federal Republic of Germany.
Bardenheuer
H
H
D000241:Adenosine / Q000494:pharmacology*; D000243:Adenosine Deaminase / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*
D005609:Free Radicals; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000243:Adenosine Deaminase; D000241:Adenosine; D010100:Oxygen; D002118:Calcium