L-selectin-mediated lymphocyte aggregation: Role of carbohydrates, activation and effects on cellular interactions

L-selectin on lymphocytes reacts with glycosylated ligands on high endothel ial venule walls in lymphoid organs. Through this carbohydrate-dependent in teraction, rolling and initial attachment of lymphocytes to endothelium is mediated. Here we have studied an earlier described L-selectin-induced homo typic aggregation, to further elucidate the events that occur after engagem ent of L-selectin. It was found that the interaction of L-selectin with fuc oidan, but not with other carbohydrates, or with monoclonal antibodies dire cted against the carbohydrate recognition domain of L-selectin, resulted in homotypic aggregation among both B- or T lymphocytes. Importantly, this ag gregation was shown to be both lymphocyte function-associated antigen-1 (LF A-1) and calcium-independent. Furthermore, for aggregation metabolic energy was required, and signalling via protein tyrosine kinase appeared to be in volved. Neither tie novo protein synthesis, protein kinase C mediated signa lling, G(i)-protein mediated signal transduction, nor calcium mobilization were required for aggregation. During aggregation, L-selectin was not shed from the lymphocyte's cell surface. Finally, it was found that the lymphocy te binding capacity to high endothelial venules on cryostat sections was no t altered upon triggering these lymphocytes via L-selectin. Interestingly, L-selectin-triggered cells showed increased binding to paracortical areas i n peripheral lymph nodes. Our data suggest that signals via L-selectin, mig ht lead to altered expression of cell surface molecules, important in inter actions other than the first Stage of lymphocyte rolling.