An Absolute Requirement for P-Selectin in Ischemia/Reperfusion-Induced Leukocyte Recruitment in Cremaster Muscle

Abstract

Objective: To systematically examine a role for P-selectin in a model of striated muscle ischemia/reperfusion (I/R). Methods: Ischemia was induced in the cremaster muscle of mice by occluding the main feeding arteriole for 30 minutes. Blood flow was then restored to allow for 60 minutes of reperfusion and leukocyte kinetics were assessed during the control period (before I/R) and at 5, 30, and 60 minutes of reperfusion. To study a role for P-selectin in this model, three different approaches were used: Wildtype animals received fucoidin (10 mg/kg, iv), an anti-P-selectin antibody (RB40.34; 20 mg/animal, iv) at 25 minutes of ischemia, or I/R was induced in P-selectin-deficient mice. Results: Ischemia/reperfusion induced a rapid and significant increase in leukocyte rolling, adhesion, and emigration in wild-type mice. The I/R-induced increase in leukocyte rolling was transient, inasmuch as it was reduced by approximately 50% at 30 minutes of reperfusion, and returned to control levels by 60 minutes. Both fucoidin and an anti-P-selectin antibody completely prevented the I/R-induced increase in leukocyte rolling. The P-selectin-deficient animals exhibited absolutely no baseline leukocyte rolling, adhesion, or emigration. Furthermore, I/R did not induce any increase in leukocyte recruitment in the Pselectin-deficient animals over the first 60 minutes of reperfusion. Conclusion:The results from this study clearly illustrate that P-selectin is absolutely critical in both baseline and I/R-induced leukocyte infiltration in the murine-striated muscle.

Therapeutic Intervention in Inflammatory Diseases: A Time and Place for Anti‐Adhesion Therapy

“…Superfusion of the mesentery for 4 h with bacterial products such as lipopolysaccharide or induc-tion of ischemia/reperfusion for prolonged periods of time demonstrated the start of a second wave of rolling in the absence of functional P-selectin that was inhibitable by immunoneutralization of E-selectin (32,66). Nevertheless, waiting a little longer (6 h) revealed that a third mechanism of leukocyte rolling could be noted, which was L-selectin dependent (42).…”

Differential Expression of E‐ and P‐Selectin in the Microvasculature of Sickle Cell Transgenic Mice

“…Several endothelial cell adhesion molecules (CAMs), including E-and P-selectin, appear to mediate the leukocyte-endothelial cell adhesion induced by acute inflammatory states such as I/R (22,26). A role for the selectins in this condition is supported by studies demonstrating an attenuated I/R-induced leukocyte adhesion in venules of mice that are genetically deficient in either E-or P-selectin (23,40) or in wild-type (WT) mice treated with blocking monoclonal antibodies (mAb) directed against a specific selectin (36). There is similar evidence implicating the selectins in the leukocyte adhesion observed in postcapillary venules of sickle cell transgenic mice.…”

Platelet, but not endothelial, P‐selectin is critical for neutrophil‐mediated acute postischemic renal failure

“…Several in vivo and in vitro studies have provided evidence for P-selectin-dependent interactions between leukocytes and endothelial cells after ischemia/reperfusion (26,27) or hypoxia/reoxygenation (28). Evidence for a role of platelet P-selectin is based on reports that neutrophils can roll on platelet P-selectin in flow chamber systems in vitro (29).…”