VLA-4 and its ligands: relevance to kidney diseases.

Alterations in cellular immunity have been implicated in many kidney diseases. The role of the adhesion molecule VLA-4 and its known ligands VCAM-1 and CS-1 have just begun to be evaluated in association with kidney diseases. VCAM-1 in human kidney is normally expressed in the Bowman's capsule, in the proximal renal tubule, and in the vascular endothelium. Up-regulation of VCAM-1 expression is seen in many different forms of glomerulonephritis as well as in a mouse model of lupus nephritis. Up-regulation of VCAM-1 expression is observed in the renal allograft with acute cellular rejection, and correlates with areas of leukocyte infiltration and vascular inflammation. CS-1 may also be up-regulated in the rejecting kidney. Animal studies on cardiac transplantation demonstrate that blockade of VLA-4 or VCAM-1 can attenuate transplant rejection. Hemodialysis patients, known to have a cellular immunodeficiency, have increased levels of soluble VCAM-1 in their serum. There is increasing evidence that there are alterations in VLA-4, VCAM-1 and CS-1 in association with kidney diseases. Further studies will be required to delineate the role of these molecules in the immunopathogenesis of select kidney diseases and the possibility of intervening in these adhesion pathways to ameliorate clinical syndromes.