Thermotolerance protects against endotoxin-mediated microvascular injury

An early event in endotoxin-induced tissue injury is adhesion and migration of leukocytes through the endothelium. This is a three-stage process, init ially low-grade selectin-mediated adhesion, seen as a decrease in rolling v elocity, followed by integrin-mediated adhesion and transmigration. Thermot olerance has been shown to reduce tissue injury and mortality induced by en dotoxin. The aim of this study was to investigate the effect of thermotoler ance on leukocyte-endothelial interactions. Intravital video microscopy was used to examine hemodynamic parameters, leukocyte rolling, adhesion, and m igration in rat mesenteric postcapillary venules. Sprague-Dawley rats were randomized into control, lipopolysaccharide (LPS), and thermotolerance + LP S groups. Thermotolerance was induced 18 h prior to administration of LPS b y elevating core body temperature to 41 + 0.5 degreesC for 15 min. LPS (055 :B5 15 mg/kg) was administered via the jugular vein after baseline recordin g. Leukocyte rolling velocity and the number of adherent and migrated leuko cytes were measured by intravital microscopy at baseline 0 min and 10, 30, 60, and 90 min after LPS administration. Heat shock protein 72 (HSP72) expr ession in tissues was determined by Western immunoblotting. The results ind icated that LPS administration significantly decreased leukocyte rolling ve locity during endotoxemia and increased leukocyte adhesion (10.3 +/- 1.67, 13.2 +/- 1.40, and 10.0 +/- 1.57/100 mum) and migration (5.7 +/- 1.02 and 8 .3 +/- 1.76/field) at 30, 60, and 90 min after LPS injection (P < 0.01 vs b aseline and control group). Thermotolerance maintained leukocyte rolling ve locity and significantly reduced leukocyte adhesion (5.7 +/- 0.88 and 4.0 /- 0.68/100 <mu>m) and migration (2.8 +/- 0.32 and 3.0 +/- 0.68/field) at 3 0 and 60 min after LPS administration (P < 0.01 and 0.05 vs LPS group). Exp ression of HSP72 was induced in mesentery, gut, and lung by thermotolerance . This study indicates that thermotolerance attenuated LPS-induced microvas cular injury by decreasing leukocyte-endothelial adhesion and migration, (C ) 2000 Academic Press.