EXPRESSION AND REGULATION OF THE NEURAL CELL-ADHESION MOLECULE L1 ON HUMAN-CELLS OF MYELOMONOCYTIC AND LYMPHOID ORIGIN

The neural cell adhesion molecule L1 has been implicated in a variety of neurologic processes, including neuritogenesis and cerebellar cell migration. Here we propose an expanded role for this cell adhesion mol ecule in the human immune system based on its expression on cells of m yelomonocytic and lymphoid origin, Freshly isolated circulating monocy tes had minimal L1 expression; however, activation of these effector c ells by IFN-gamma, or as a result of density gradient isolation, resul ted in a significant induction of L1 expression. Constitutive L1 expre ssion was further evident on myelomonocytic cell lines but was absent on mature tissue macrophages. In further studies, positive selection w ith a L1-specfic Ab enriched both B cells and dendritic precursor cell s from peripheral blood, Significantly, L1 expression was not deteted on mature dendritic cells but could be induced by treatment with LPS, PHA, and TNF-alpha, Immunohistochemical analysis further demonstrated significant L1 expression on follicular dendritic cells and on endothe lial cells associated with the arterioles and red pulp of normal splee n. Based on these observations and known functions of L1, we propose t hat this cell adhesion molecule may contribute to cell-cell adhesion e vents associated with the effector function or extravasation of these immune effector cells. In support of the latter,we present evidence th at L1 can be recognized by endothelial cells via the integrin alpha(v) beta 3.