Hemodialysis-lnduced Upregulation of Granulocyte Adhesion Molecules CD 11b/CD18 Is Independent from 5-Lipoxygenase Activity

Abstract

Hemodialysis with new cuprophane membranes upregulates expression of granulocyte adhesion molecules and activates 5-lipoxygenase as reflected by the enhanced generation of leukotriene B₄ (LTB₄). We assessed the role of 5-lipoxygenase activity in hemodialysis-induced upregulation of the granulocyte adhesion molecules, CD lib and CD 18, and granulocyte adhesion to human umbilical vein endothelial cells in an ex vivo dialysis model. 5-Lipoxygenase was effectively inhibited by preincubation of human whole blood with the speciñc inhibitor, BAY XI00 5. Dialysis with new cuprophane but not with new acrylonitrile membranes significantly upregulated expression of CD1 lb and CD 18 by 6-fold and 4-fold, respectively. Inhibition of 5-lipoxygenase did not affect the expression of CD1 lb and CD 18 during dialysis with either of the two membranes. In contrast to the enhanced expression of CD1 lb and CD 18, adhesion of granulocytes to human umbilical vein endothelial cells did not increase during dialysis, nor was it affected by BAY XI005. These data indicate that ex vivo dialysis with cuprophane membranes upregulates expression of CD1 lb and CD 18 on granulocytes independent of the activation of 5-lipoxygenase.

Low Density Lipoprotein (LDL) Modification: Basic Concepts and Relationship to Atherosclerosis

“…High susceptibility to oxidation reported in LDL from HD patients [67] can be also due to the high proportion of LDL -which promotes oxidation of the remaining LDL [5]. The involvement of LDL -in the induction of proinflammatory pathways is suggested since paradoxically high eicosanoid production [70], over-expression of scavenger receptors [71], adhesion molecules [72], MCP-1 and other cytokines [72] in peripheral blood mononuclear cells have been reported in HD patients. Moreover, uremic serum can increase the scavenger receptor expression and activity in the human monocytic cell line U937 [73].…”