Monocyte chemoattractant protein-1 enhances expression of intercellular adhesion molecule-1 following ischemia-reperfusion of the liver in rats

Abstract

Neutrophils mediate microvascular and parenchymal cell dysfunction in a variety of organs after ischemia-reperfusion. 1,2 Reperfusion of ischemic tissue results in the formation of proinflammatory mediators that promote the adherence and emigration of neutrophils in postcapillary venules. 3 The activated neutrophils subsequently injure tissue by releasing oxidants and proteases. 4,5 This hypothesis is based largely on studies demonstrating that tissue injury induced by ischemia-reperfusion is attenuated by rendering the animals neutropenic with antineutrophil serum. 6,7 Additional support for this view is derived from several studies showing that monoclonal antibodies against either the CD11a or CD11b ␣ subunits of the CD11/CD18 on neutrophils 8,9 or intercellular adhesion molecule-1 (ICAM-1) on endothelial cells 10 afford significant protection against ischemia-reperfusion injury. Thus, ICAM-1 is important for the development of a neutrophil-dependent injury mechanism.Alterations in the endothelial cell in response to cytokines may be of critical importance in interactions between circulating leukocytes and the vessel wall, because changes in the expression of adhesion receptors may regulate the number and type of leukocytes emigrating from the blood into inflamed tissues. 11 Tumor necrosis factor ␣, interleukin-1, and interferon gamma have been reported to induce the production of ICAM-1 message and protein in isolated murine hepatocytes, 12 human hepatocytic cell lines, 13 and endothelial cells. 14,15 These observations suggest that ICAM-1 expression may be induced by other proinflammatory cytokines.Monocyte chemoattractant protein 1 (MCP-1), originally described as the JE gene, is a 148-amino acid chemotactic cytokine [16][17][18] that is expressed by a number of cells including monocytes, leukocytes, fibroblasts, endothelial cells, smooth muscle cells, chondrocytes, and pulmonary epithelial cells. [16][17][18][19][20] Jiang et al. 21 and Vaddi et al. 22 demonstrated that MCP-1 induced expression of CD11c (p150,95, ␣-subunit) and CD11b (Mac-1 ␣-subunit), suggesting that MCP-1 is not only a chemoattractant, but also a cytokine with the capacity to regulate monocyte function. Thus, MCP-1 may modulate leukocyte-endothelial cell interactions, specifically by affecting ICAM-1 expression. Kupffer cells generate a wide range of inflammatory mediators including cytokines, eicosanoids, reactive oxygen intermediates, and other factors. The production of several cytokines following Kupffer cell activation may be important in the pathophysiology of liver ischemiareperfusion injury. Therefore, the present study was undertaken to investigate the effects of MCP-1 produced by Kupffer cells on ICAM-1 expression after ischemia-reperfusion of the rat liver. MATERIALS AND METHODSAnimals. Male Wistar rats were obtained from a commercial supplier (Kyudo, Inc., Kumamoto, Japan). All animals were maintained under standard conditions and were fed water and rodent chow ad libitum. The animals weighed between 225 and 250 g.Preparatio...

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