Ischemic preconditioning prevents postischemic P-selectin expression in the rat small intestine

Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, School of Medicine in Shreveport, Shreveport, Louisiana 71130 Ischemic preconditioning (IPC) prevents the deleterious effects of prolonged ischemia and reperfusion (I/R). Because leukocyte infiltration is required to produce the microvascular dysfunction induced by I/R in the small intestine, and P-selectin-dependent leukocyte rolling is a requisite step in this process, we hypothesized that IPC would attenuate postischemic P-selectin expression. To address this postulate, P-selectin expression was evaluated in nonischemic (control) rat jejunum and in rat jejunum subjected to I/R alone (20 min ischemia/60 min reperfusion), or IPC (5 min ischemia/10 min reperfusion) + I/R using a dual radiolabeled monoclonal antibody approach. I/R was associated with a sevenfold increase in jejunal P-selectin expression, an effect that was completely abolished by IPC. Exposing the bowel to adenosine deaminase or an adenosine A 1 , but not an A 2 , receptor antagonist during the period of preconditioning ischemia or to selective PKC antagonists during prolonged ischemia prevented the beneficial effect of IPC to limit I/R-induced P-selectin expression. Our data indicate that P-selectin expression is a novel downstream effector target of the adenosine-initiated, PKC-dependent, anti-inflammatory signaling pathway in IPC. ischemia; reperfusion; adenosine; protein kinase C; leukocyte rolling