Leukocyte and endothelial cell adhesion molecules in a chronic murine model of myocardial reperfusion injury

Academic Article


  • Expression of endothelial and leukocyte cell adhesion molecules is a principal determinant of polymorphonuclear neutrophil (PMN) recruitment during inflammation. It has been demonstrated that pharmacologi-cal inhibition of these molecules can attenuate PMN influx and subsequent tissue injury. We determined the temporal expression of α-granule membrane protein-40 (P-selectin), endothelial leukocyte adhesion molecule I (E-selectin), and intercellular cell adhesion molecule 1 (ICAM-1) after coro-nary artery occlusion and up to 3 days of reperfusion. The expression of all of these cell adhesion molecules peaked around 24 h of reperfusion. We determined the extent to which these molecules contribute to PMN infiltration by utilizing mice deficient (-/-) in P-selectin, E-selectin, ICAM-1, and CD18. Each group underwent 30 min of in vivo, regional, left anterior descending (LAD) coronary artery is-chemia and 24 h of reperfusion. PMN accumulation in the ischemic-reperfused (I/R) zone was assessed using histologi-cal techniques. Deficiencies of P-selectin, E-selectin, ICAM-1, or CD18 resulted in significant (P < 0.05) attenuation of PMN infiltration into the I/R myocardium (MI/R). In addi-tion, P-selectin, E-selectin, ICAM-1, and CD18 -/- mice exhibited significantly (P < 0.05) smaller areas of necrosis after MI/R compared with wild-type mice. These data dem-onstrate that MI/R induces coronary vascular expression of P-selectin, E-selectin, and ICAM-1 in mice. Furthermore, genetic deficiency of P-selectin, E-selectin, ICAM-1, or CD18 attenuates PMN sequestration and myocardial injury after in vivo MI/R. We conclude that P-selectin, E-selectin, ICAM-1, and CD18 are involved in the pathogenesis of MI/R injury in mice.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Jones SP; Trocha SD; Strange MB; Granger DN; Kevil CG; Bullard DC; Lefer DJ
  • Volume

  • 279
  • Issue

  • 5 48-5