Vascular adhesion protein-1 (VAP-1) mediates lymphocyte-endothelial interactions in chronic kidney rejection.
The pathogenesis of chronic kidney rejection characterized by persistent low-level inflammation and intimal thickening of the arteries in the graft remains poorly understood. We studied whether two important endothelial adhesion molecules, vascular adhesion molecule-1 (VAP-1) and peripheral node addressin (PNAd), would contribute to the lymphocyte recruitment into the rejected organ. VAP-1 was found to be present both in the normal kidney and prominently also in the chronically rejected kidneys. In the kidney VAP-1 was a homodimeric sialoglycoprotein expressed in peritubular capillaries, but not on glomerular endothelium or on tubular cells. In contrast, PNAd was absent from all kidney samples, indicating that kidney inflammation differs from other sites of chronic inflammation. Blocking of VAP-1 with mAbs abolished > 50 % of lymphocyte binding to renal vessels in rejected kidney in in vitro adhesion assays. Levels of circulating soluble VAP-1 (sVAP-1) decreased back to normal levels in patients with well-functioning transplants. These results are the first evidence that VAP-1 is able to mediate leukocyte binding into a rejected organ. Thus, anti-adhesive therapies targeting VAP-1 may be useful in controlling chronic kidney graft rejection.
Kurkijärvi
R
R
MediCity Research Laboratory, University of Turku and National Public Health Institute, Department in Turku, Turku, Finland.
Jalkanen
S
S
Isoniemi
H
H
Salmi
M
M
D006631:Amine Oxidase (Copper-Containing) / Q000032:analysis / Q000502:physiology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000502:physiology*; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000166:cytology*; D006084:Graft Rejection; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007668:Kidney / Q000737:chemistry; D016030:Kidney Transplantation; D008214:Lymphocytes / Q000502:physiology*; D014184:Transplantation, Homologous
D015815:Cell Adhesion Molecules; D018799:Intercellular Adhesion Molecule-1; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)