BETA-ADRENERGIC MODULATION OF FMLP-INDUCED AND ZYMOSAN-INDUCED INTRACELLULAR AND EXTRACELLULAR OXIDANT PRODUCTION BY POLYMORPHONUCLEAR LEUKOCYTES

Evaluation of catecholamine modulation of PMNL extracellular and intra cellular oxidant production may reflect beneficial and harmful effects of P-adrenergic agonists in various disease states. We investigated t he kinetics and potency of adrenaline-mediated inhibition of oxidant g eneration in FMLP- and zymosan-stimulated PMNLs. In FMLP-stimulated ce lls, the shortterm burst of oxidant generation was inhibited by adrena line in a dose-dependent fashion. Intra- and extracellular chemilumine scence and extracellular superoxide anion and hydrogen peroxide genera tion showed similar IC,, values for adrenaline (1.3-3.0 x 10(-8) M) in dicating that both extracellular and intracellular events were inhibit ed with the same potency. In contrast, intracellular oxidant productio n evoked by the phagocytosis of zymosan was only minimally affected by 3 x 10(-5) - 3 X 10(-12) M adrenaline. Extracellular inhibition of ox idant production was also apparent in zymosan-stimulated cells. In con clusion, adrenaline's ability to depress extracellular generation of o xygen metabolites while retaining prolonged intracellular oxidant prod uction for phagocytosis supports its beneficial role as selectively ta rgeted physiological protector.