Vascular adhesion protein-1 (VAP-1) mediates lymphocyte-endothelial interactions in chronic kidney rejection

The pathogenesis of chronic kidney rejection characterized by persistent lo w-level inflammation and intimal thickening of the arteries in the graft re mains poorly understood. We studied whether two important endothelial adhes ion molecules, vascular adhesion molecule-1 (VAP-1) and peripheral node add ressin (PNAd), would contribute to the lymphocyte recruitment into the reje cted organ. VAP-1 was found to be present both in the normal kidney and pro minently also in the chronically rejected kidneys. In the kidney VAP-1 was a homodimeric sialoglycoprotein expressed in peritubular capillaries, but n ot on glomerular endothelium or on tubular cells. In contrast, PNAd was abs ent from all kidney samples, indicating that kidney inflammation differs fr om other sites of chronic inflammation. Blocking of VAP-1 with mAbs abolish ed > 50 % of lymphocyte binding to renal vessels in rejected kidney in in v itro adhesion assays. Levels of circulating soluble VAP-1 (sVAP-1) decrease d back to normal levels in patients with well-functioning transplants. Thes e results are the first evidence that VAP-1 is able to mediate leukocyte bi nding into a rejected organ. Thus, antiadhesive therapies targeting VAP-1 m ay be useful in controlling chronic kidney graft rejection.