Endothelial L-selectin ligands are likely to recruit lymphocytes into rejecting human heart transplants

L-selectin-dependent lymphocyte extravasation is a hallmark of acute heart allograft rejection in rats. On screening over 600 endomyocardial biopsies (EMBs), taken at different time points after heart transplantation in man, we identified 91 samples with histological signs of acute rejection. Reject ion and nonrejection EMBs were analyzed for the presence of properly glycos ylated, ie, sulfated sialyl Lewis-x (sLex) decorated L-selectin ligands, Tw o anti-sLex (2F3 and HECA-452) and one anti-6- or 6'-sulfated and/or 6,6'-b isulfation (MECA-79) monoclonal antibodies were used. Nonrejecting heart en dothelium did not express, or expressed only weakly, sulfated and or sLex d ecorations of L-selectin ligands. On the contrary, these epitopes were read ily detectable on endothelium of capillaries and venules at the onset and d uring acute rejection episodes. The more intense the sulfated sLex expressi on was, the more severe the rejection episode was in histological grading. The endothelial expression of L-selectin ligands decreased to background le vels as the rejection resolved, Our data demonstrate a complete correlation between the level of expression of the sulfated sLex-decorated ligands on the one hand and the histological severity of acute heart allograft rejecti on on the other hand. These data suggest that functionally active endotheli al L-selectin ligands are instrumental in lymphocyte extravasation into the human heart allografts at the onset and during acute rejection episodes.