Expression of cell adhesion molecules in primary renal disease and renal allograft rejection.

IL-1: interleukin 1; MHC: major histocompatibility complex; PECAM-1: platelet endothelial cell adhesion Background. In vitro studies have demonstrated that inflammatory mediators such as the cytokines TNFa molecule-1; TNFa: tumour necrosis factor a; VCAM-1: vascular cell adhesion molecule-1. and IL-1 upregulate or induce de novo expression of cell adhesion molecules on endothelial and epithelial cells. In the present study the expression of the cell adhesion molecules ICAM-1, VCAM-1, E-selectin and Introduction PECAM-1 was investigated in renal biopsies from patients with primary renal diseases (n=66) and from Infiltration of the renal parenchyma with inflammatory renal allograft recipients (n=42). cells, including lymphocytes, monocytes, and granuloMethods. Expression of the cell adhesion molecules cytes characterizes the histological picture of inflamwas determined by immunohistochemistry of frozen matory kidney diseases, autoimmune disorders and sections using monoclonal antibodies directed against renal allograft rejection [1,2]. PECAM-1, ICAM-1, VCAM-1, E-selectin and MHC In the earliest stages of inflammatory processes, class II molecules (APAAP method). leukocytes interact with the endothelial cell lining of Results and Conclusions. PECAM-1 and ICAM-1 were the vasculature [3 ]. Endothelial cell injury promotes expressed in the renal vasculature and disappeared in endothelial cell— leukocyte interaction that is mediated obliterated glomeruli with endothelial cell destruction. by cell surface adhesion molecules to support leukocyte ICAM-1 but not PECAM-1 was upregulated in renal adhesion and transmigration [4]. E-selectin, which endothelia in acute allograft rejection and inflammat- belongs to the selectin family, turns up very early in ory primary renal diseases. Tubular de novo expression the inflammatory process. It binds to sialylated glycoof ICAM-1 and VCAM-1 correlated with severe struc- proteins on leukocytes to promote the weak attraction tural damage of the renal parenchyma including inter- and rolling of leukocytes on endothelial cells [5 ]. The stitial fibrosis. Vascular and/or glomerular VCAM-1 immunoglobulin-like molecules ICAM-1 and VCAM-1 and E-selectin expression was pronounced in severe are responsible for the firm secondary endothelial acute allograft rejection and also reflected the intensity cell—leukocyte adhesion followed by transmigration of inflammatory reactions in primary renal diseases of leukocytes through the endothelial cell lining [6 ]. with or without autoimmune disorders. De novo expres- ICAM-1, which binds to the b2-integrins LFA-1 and sion of VCAM-1 and E-selectin in renal vessels and/or Mac-1 on leukocytes is expressed constitutively on glomeruli and overexpression of ICAM-1 are markers endothelial cells and leukocytes and upregulated by of acute and severe inflammatory processes in biopsies cytokines, such as IL-1 and TNFa [7]. VCAM-1 from allograft recipients and patients with primary expression is induced by cytokines on activated endorenal diseases. thelial cells and some epithelial cells and binds to the b1-integrin VLA-4 [8 ]. Furthermore, ICAM-1 and