S. Kanwar et al., An absolute requirement for P-selectin in ischemia/reperfusion-induced leukocyte recruitment in cremaster muscle, MICROCIRCUL, 5(4), 1998, pp. 281-287
Objective: To systematically examine a role for P-selectin in a model of st
riated 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 du
ring the control period (before I/R) and at 5, 30, and 60 minutes of reperf
usion. To study: a role for P-selectin in this model. three different appro
aches were used: Wild-type animals received fucoidin (10 mg/kg, iv), an ant
i-P-selectin antibody (RB40.34; 20 mg/animal, iv) at 25 minutes of ischemia
, or I/R mas induced in P-selectin-deficient mice.
Results: Ischemia/reperfusion induced a rapid and significant increase in l
eukocyte rolling, adhesion, and emigration in wild-type mice. The I/R-induc
ed 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 complet
ely prevented the I/R-induced increase in leukocyte rolling. The P-selectin
-deficient animals exhibited absolutely no baseline leukocyte rolling, adhe
sion, or emigration. Furthermore, I/R did not induce any increase in leukoc
yte recruitment in the P-selectin-deficient animals over the first 60 minut
es of reperfusion.
Conclusion: The results from this study clearly illustrate that P-selectin
is absolutely critical in both baseline and I/R-induced leukocyte infiltrat
ion in the murine-striated muscle.