Preconditioning and adenosine in I/R-induced leukocyte-endothelial cell interactions

Abstract

Recently, it was reported that preconditioning reduced leukocyte adhesion following ischemia-reperfusion (I/R). We further examined the effects of preconditioning and adenosine not only on neutrophil adhesion but also on neutrophil rolling and vascular dysfunction. Intravital microscopy revealed a decrease in neutrophil rolling velocity; a profound increase in neutrophil rolling, adhesion, and microvascular dysfunction; and a reduction in venular shear rates associated with 60 min ischemia and 60 min reperfusion in the feline mesentery. Preconditioning (5 min ischemia/10 min reperfusion) prevented subsequent I/R-induced slow neutrophil rolling, neutrophil adhesion, and microvascular dysfunction but did not affect the flux of rolling neutrophils. Adenosine deaminase A1 and A2 adenosine-receptor antagonists had only minor effects on the preconditioning responses. Pretreatment of vessels with exogenous adenosine reduced neutrophil adhesion and microvascular permeability and improved neutrophil rolling velocity and shear forces associated with I/R, but the flux of rolling neutrophils was not affected. Finally, in vitro experiments revealed that adenosine had absolutely no direct effect on neutrophil-endothelial cell interactions. In conclusion, our data suggest that adenosine plays only a minor role in preconditioned vessels and that adenosine per se may not directly affect neutrophil-endothelial cell interactions.