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 superoxi de anions (O-2(-)). 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 o f hyperdynamic endotoxemia. Ten anesthesized pigs received an intraven ous (i.v.) 330-min infusion of endotoxin (5 mu g/kg of body weight per h). Another 10 pigs were also infused with endotoxin plus adenosine ( 150 mu g/kg/min [i.v.]); this treatment was begun 30 min Drier to the beginning of endotoxin treatment, Control groups (five animals per gro up) received either adenosine or physiological saline, Infusion of end otoxin caused severe neutropenia, shedding of L-selectin, upregulation of beta(2)-integrins, increased binding of C3-coated zymosan particle s, and subsequent phagocytosis by PMNL. While phagocytosis-induced pro duction of oxygen radicals appeared to decrease, extracellular release of superoxide anions was strongly enhanced, Infusion of adenosine dur ing endotoxemia had no effect on neutropenia, expression of adhesion m olecules, C3-induced adhesion, phagocytosis, or intracellular producti on of oxygen radicals, whereas extracellular release of O-2(-) was str ongly inhibited, Thus, i.v. infusion of adenosine during endotoxemia c ould be useful in protecting from O-2(-)-mediated tissue injury withou t compromising the bactericidal mechanisms of PMNL.