Beta-adrenergic modulation of FMLP- and zymosan-induced intracellular and extracellular oxidant production by polymorphonuclear leukocytes.
Evaluation of catecholamine modulation of PMNL extracellular and intracellular oxidant production may reflect beneficial and harmful effects of beta-adrenergic agonists in various disease states. We investigated the kinetics and potency of adrenaline-mediated inhibition of oxidant generation in FMLP- and zymosan-stimulated PMNLs. In FMLP-stimulated cells, the short-term burst of oxidant generation was inhibited by adrenaline in a dose-dependent fashion. Intra- and extracellular chemiluminescence and extracellular superoxide anion and hydrogen peroxide generation showed similar IC50 values for adrenaline (1.3-3.0 x 10(-8) M) indicating that both extracellular and intracellular events were inhibited with the same potency. In contrast, intracellular oxidant production evoked by the phagocytosis of zymosan was only minimally affected by 3 x 10(-5) -3 x 10(-12) M adrenaline. Extracellular inhibition of oxidant production was also apparent in zymosan-stimulated cells. In conclusion, adrenaline's ability to depress extracellular generation of oxygen metabolites while retaining prolonged intracellular oxidant production for phagocytosis supports its beneficial role as selectively targeted physiological protector.
Kopprasch
S
S
Technical University of Dresden, Carl Gustav Carus Medical School, Department of Internal Medicine III, Germany.
Gatzweiler
A
A
Graessler
J
J
Schröder
H E
HE
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism*; D017382:Reactive Oxygen Species; D016897:Respiratory Burst / Q000187:drug effects; D015054:Zymosan / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D016877:Oxidants; D017382:Reactive Oxygen Species; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015054:Zymosan