Soluble intercellular adhesion molecule-1 (sICAM-1) after kidney transplantation: The origin and role of urinary sICAM-1?

Background. Intercellular adhesion molecule-1 (ICAM-1) binds to leukocyte a dhesion receptors LFA-I and MAC-I, and mediates leukocyte adhesion to targe t structures. During acute rejection there is increased expression of ICAM- 1 in vascular and tubulointestial cells, and consequently accumulation of i nflammatory leukocytes, Soluble ICAM-1 (sICAM-1) is released from ICAM-1 ex pressing cells and excreted into the surrounding fluid. Increased serum sIC AM-1 levels are found in patients with acute rejections of various allograf ts, and high urinary levels in steroid resistant acute kidney allograft rej ection. Methods. Urinary excretion of sICAM-1 was measured by EPA in 136 kidney all ograft recipients during the first 1-6 post transplant weeks: 30 patients d evel oped acute rejection, and 106 patients had stable graft function. The molecular weight, binding to hyaluronan, and the origin of urinary sICAM-1 were studied. Results. We show that urinary sICAM-1 circulates as a monomer with a molecu lar weight between 50 and 100 kD, It binds to immobilized, but not to circu lating hyaluronan, About one week after transplantation the mean sICAM-1/cr eatinine ratio (306 ng/mmol) in transplanted patients was higher than in th e healthy controls (167 ng/mmol, P <0.01), and remained basically unchanged during the follow-up in patients with stable graft function, whereas it in creased in patients developing rejection, being about 2.5-fold above the in itial level a few days before rejection (P<0.01), Urinary sICAM-1 did not c orrelate with the urinary albumin, whereas in patients developing rejection it correlated with urinary IL-2R (r=0.5146, P<0.001), a marker of lymphocy te activation. In the urinary sediment of rejecting patients ICAM-1 was dem onstrated in the tubular epithelial cells, and in the macrophages. Conclusions. Increased urinary excretion of sICAM-1 was demonstrated in kid ney transplanted patients a few days before acute rejection. It seems to or iginate from activated macrophages and/or from the tubular epithelial cells . The fact that urinary sICAM-1 is not bound to hyaluronan or to leukocytes suggests that it is not able to compete with membrane-bound ICAM-1.