Expression of E-Selectin in Ischemic and Reperfused Human Skeletal Muscle

Abstract

This work was undertaken to assess the role of endothelial E-selectin in the development of neutrophil accumulation into the ischemic and reperfused human skeletal muscle and eventually in the genesis of ischemia-reperfusion syndrome. Twelve patients affected by abdominal aortic aneurysm who were undergoing reconstructive vascular surgery were studied. Muscle biopsies from the right femoral quadriceps were taken (1) immediately after anesthesia, as control samples, (2) before declamping the aorta, as ischemic samples, and (3) 30 minutes after reperfusion and then processed for immunohistochemical and ultrastructural analysis. Immunohistochemistry revealed a strong positive reaction for E-selectin on the venular endothelium during ischemia and reperfusion. Ultrastructural investigation showed that reactivity for E-selectin matched neutrophil accumulation of the skeletal muscle tissue. This phenomenon was dependent upon a complex series of events that included neutrophil adhesion to the inner surface of the postcapillary venules, passage 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 O2 free radicals. Our data suggest that E-selectin expression on the vascular endothelium of human skeletal muscle may represent a key regulatory point in the process of neutrophil tissue accumulation and indicate an active role for the venular endothelium in the development of human ischemia-reperfusion syndrome.

The proteasomal system

“…The main events in stroke are the ischemic brain injury, primary generating oxidative stress, releasing cytokines activating the nuclear factor jB (NF-jB), followed by the secondary reactions in affected cells, the activation of inflammatory genes inducing the excretion of cytokines and adhesion molecules. Adhesion molecules (like the endothelial VCAM-1 (Norman et al, 2008;Zerfaoui et al, 2008), ICAM-1 (Montecucco et al, 2009;Marino et al, 2008) and E-selectin (Formigli et al, 1995;Takeda et al, 2002;Piconi et al, 2004)) fulfill a messenger function directing monocytes and leukocytes to cells and tissues that express inflammatory response. These secondary cellular reactions can induce further damage in a cascade that involves the UPS as a triggering and regulating system.…”

Ischaemia-Reperfusion Injury and Regional Inflammatory Responses in Abdominal Aortic Aneurysm Repair

“…Further research by the same group 45 in another cohort of AAA patients, took the histological examinations a step further in order to investigate the role of the vascular endothelium in response to ischaemia and reperfusion. Using immunohistochemical techniques, the presence of E-selectin upregulation (a marker of endothelial activation) during ischaemia was demonstrated when compared to control samples from the same patients prior to aortic clamping.…”

Protective effects of some antineoplastic agents on ischemia-reperfusion injury in epigastric island skin flaps

“…[37][38][39] There is evidence that neutrophils accumulate in various tissues and organs during reperfusion. 1,6,40 It was shown that activated neutrophils become ''sticky'' and are more adherent to the endothelium of tissues and organs subjected to reperfusion injury and inflammation. 9,18,41 Given the important role that neutrophils play in ischemia-reperfusion injury, it is reasonable to hypothesize that decreasing these cells with antineoplastic agents could affect the survival of ischemic tissue.…”