This work was undertaken to assess the role of endothelial E-selectin
in the development of neutrophil accumulation into the ischemic and re
perfused human skeletal muscle and eventually in the genesis of ischem
ia-reperfusion syndrome. Twelve patients affected by abdominal aortic
aneurysm who were undergoing reconstructive vascular surgery were stud
ied. Muscle biopsies from the right femoral quadriceps were taken (1)
immediately after anesthesia, as control samples, (2) before declampin
g the aorta, as ischemic samples, and (3) 30 minutes after reperfusion
and then processed for immunohistochemical and ultrastructural analys
is. Immunohistochemistry revealed a strong positive reaction for E-sel
ectin on the venular endothelium during ischemia and reperfusion. Ultr
astructural investigation showed that reactivity for E-selectin matche
d neutrophil accumulation of the skeletal muscle tissue. This phenomen
on was dependent upon a complex series of events that included neutrop
hil adhesion to the inner surface of the postcapillary venules, passag
e through endothelial intercellular junctions, and migration distally
into the interstitial spaces of the skeletal muscle tissue. Neutrophil
tissue infiltration was also associated with ultrastructural signs of
tissue damage at reperfusion. This is in agreement with accumulating
evidence indicating a role for tissue infiltrating neutrophils in the
genesis of toxic O-2 free radicals. Our data suggest that E-selectin e
xpression on the vascular endothelium of human skeletal muscle may rep
resent a key regulatory point in the process of neutrophil tissue accu
mulation and indicate an active role for the venular endothelium in th
e development of human ischemia-reperfusion syndrome.