Effects of adenosine on the functions of circulating polymorphonuclear leukocytes during hyperdynamic endotoxemia.
Endotoxin-activated polymorphonuclear leukocytes (PMNL) adhere to the vascular endothelium and cause damage by the release of toxic superoxide anions (O2-). Because adenosine is a potent inhibitor of PMNL in vitro, the present study investigates the effects of this nucleoside on the functions of circulating PMNL in a standardized porcine model of hyperdynamic endotoxemia. Ten anesthesized pigs received an intravenous (i.v.) 330-min infusion of endotoxin (5 microg/kg of body weight per h). Another 10 pigs were also infused with endotoxin plus adenosine (150 microg/kg/min [i.v.]); this treatment was begun 30 min prior to the beginning of endotoxin treatment. Control groups (five animals per group) received either adenosine or physiological saline. Infusion of endotoxin caused severe neutropenia, shedding of L-selectin, upregulation of beta2-integrins, increased binding of C3-coated zymosan particles, and subsequent phagocytosis by PMNL. While phagocytosis-induced production of oxygen radicals appeared to decrease, extracellular release of superoxide anions was strongly enhanced. Infusion of adenosine during endotoxemia had no effect on neutropenia, expression of adhesion molecules, C3-induced adhesion, phagocytosis, or intracellular production of oxygen radicals, whereas extracellular release of O2- was strongly inhibited. Thus, i.v. infusion of adenosine during endotoxemia could be useful in protecting from O2(-)-mediated tissue injury without compromising the bactericidal mechanisms of PMNL.
Thiel
M
M
Institute for Surgical Research and Department of Anesthesiology, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Germany.
Holzer
K
K
Kreimeier
U
U
Moritz
S
S
Peter
K
K
Messmer
K
K
D015762:2-Chloroadenosine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D018821:CD18 Antigens / Q000032:analysis; D019446:Endotoxemia / Q000276:immunology*; D005260:Female; D019041:L-Selectin / Q000032:analysis; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D013552:Swine
D018821:CD18 Antigens; D013481:Superoxides; D019041:L-Selectin; D015762:2-Chloroadenosine; D000241:Adenosine