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 adhesion receptors LFA-1 and MAC-1, and mediates leukocyte adhesion to target structures. During acute rejection there is increased expression of ICAM-1 in vascular and tubulointestial cells, and consequently accumulation of inflammatory leukocytes. Soluble ICAM-1 (sICAM-1) is released from ICAM-1 expressing cells and excreted into the surrounding fluid. Increased serum sICAM-1 levels are found in patients with acute rejections of various allografts, and high urinary levels in steroid resistant acute kidney allograft rejection.


METHODS
Urinary excretion of sICAM-1 was measured by EIA in 136 kidney allograft recipients during the first 1-6 post transplant weeks: 30 patients developed 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 molecular weight between 50 and 100 kD. It binds to immobilized, but not to circulating hyaluronan. About one week after transplantation the mean sICAM-1/creatinine ratio (306 ng/mmol) in transplanted patients was higher than in the healthy controls (167 ng/mmol, P<0.01), and remained basically unchanged during the follow-up in patients with stable graft function, whereas it increased in patients developing rejection, being about 2.5-fold above the initial level a few days before rejection (P<0.01). Urinary sICAM-1 did not correlate with the urinary albumin, whereas in patients developing rejection it correlated with urinary IL-2R (r=0.5146, P<0.001), a marker of lymphocyte activation. In the urinary sediment of rejecting patients ICAM-1 was demonstrated in the tubular epithelial cells, and in the macrophages.


CONCLUSIONS
Increased urinary excretion of sICAM-1 was demonstrated in kidney transplanted patients a few days before acute rejection. It seems to originate 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 for these bindings, but may do so for the binding of activated macrophages.
Teppo
A M
AM
Department of Medicine, Helsinki University Hospital , Finland.
von Willebrand
E
E
Honkanen
E
E
Ahonen
J
J
Grönhagen-Riska
C
C
D000419:Albuminuria; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003404:Creatinine / Q000652:urine; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000175:diagnosis* / Q000473:pathology / Q000652:urine; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000652:urine*; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008262:Macrophage Activation; D015375:Receptors, Interleukin-2 / Q000032:analysis; D012016:Reference Values; D013997:Time Factors; D014184:Transplantation, Homologous
D015415:Biomarkers; D015375:Receptors, Interleukin-2; D018799:Intercellular Adhesion Molecule-1; D003404:Creatinine