Superoxide mediates reperfusion-induced leukocyte-endothelial cell interactions

Abstract

The objective of this study was to determine whether superoxide mediates the leukocyte-endothelial cell interactions elicited by reperfusion (reoxygenation) of ischemic (hypoxic) tissues. Mesenteric and intestinal blood flows were reduced to 20% of control for 1 h, followed by 1 h of reperfusion. Sixty minutes after reperfusion, red blood cell velocity (Vr), leukocyte rolling velocity (Vw), and the number of adherent leukocytes were measured in mesenteric venules. Then, either human superoxide dismutase (hSOD), hydrogen peroxide-inactivated hSOD, or MoAb IB4 (a monoclonal antibody against the leukocyte adhesion molecule CD18) was injected intravenously. Ten minutes later, repeat measurements were obtained and compared with pretreatment values. hSOD attenuated reperfusion-induced neutrophil adherence and increased Vw/Vr, an index of the fracture stress between leukocytes and endothelium. Peroxide-inactivated hSOD did not alter any parameter. MoAb IB4 attenuated reperfusion-induced adherence but did not alter Vw/Vr. In a correlate study, cultured bovine microvascular endothelium was exposed to 30 min of anoxia, followed by 60 min of reoxygenation. Cat neutrophils were added during reoxygenation. Reoxygenation-induced leukocyte adherence was attenuated by either hSOD or MoAb IB4 but not by inactivated hSOD. Adherence of phorbol 12-myristate 13-acetate-activated cat neutrophils to plastic was unaffected by hSOD or inactive hSOD, yet MoAb IB4 virtually abolished the response. These results indicate that superoxide mediates reperfusion-induced leukocyte adherence and that endothelial cells are required for this superoxide-mediated adherence.

Interactive role of nitric oxide and superoxide anion in neutrophil-mediated endothelial cell injury

“…In this context, the interaction of NO with oxygen free radicals, particularly with O 2 Ϫ , is of significance. The capacity of SOD to (1) reverse adhesion in mesentric venules caused by ischemia-reperfusion [34], (2) attenuate the effect of xanthine-xanthine oxidase-induced adherence of PMN [35], and (3) potentiate inhibition of PMN aggregation [36], are a few observations supporting the view that O 2 Ϫ modulates leukocyte adhesion to EC. Although the exact mechanism by which O 2 Ϫ mediates PMN-EC adhesion is poorly defined, it may be speculated that O 2 Ϫ neutralizes the anti-adhesive substance released from EC.…”

Ischemia-reperfusion injury in rats affects hydraulic conductivity in two phases that are temporally and mechanistically separate

“…Because the excess elaboration of ROS is a primary component of IR that damages numerous biological molecules, including amino acids, cytochrome enzymes, transport proteins, and nucleic acids (18,19), it seemed likely that ROS were involved in the IR-induced biphasic increase we saw in microvascular permeability. Additional evidence for this likelihood is that, after an ischemia event, ROS are produced immediately during reperfusion (32,33).…”

Polyethylene Glycol-Conjugated Superoxide Dismutase Improves Recovery of Postischemic Hypercapnic Cerebral Blood Flow in Piglets

“…rhese data in combination with the finding of improved recovery )f CBF response to hypercapnia without improved recovery of :lectrical function suggest that in this study the site of action of ?EG-SOD is in the vascular compartment. For example, SOD nay act to prevent oxygen radical injury to cerebral arterioles 19), prevent superoxide anion-induced platelet adhesion (26), )r prevent superoxide-mediated leukocyte-endothelial cell adlerence (27).…”