LIGAND-BINDING SPECIFICITY OF A MACROPHAGE SURFACE-RECEPTOR UTILIZED BY THE FLUORESCEIN HAPTEN FOR UPTAKE INTO THE ENDOCYTIC PATHWAY

A series of compounds were tested as inhibitors of receptor-binding an d uptake of fluorescein-derivatized antigens in primary peritoneal and J774 murine macrophage. Results were analysed with regard to the inhi bitory potency of the tested ligands and revealed that the putative ce ll surface receptor preferentially recognized and bound aromatic struc tures containing phenyl rings. L-phenylalanine was found to be the mos t potent inhibitor among the ligands tested. Significant inhibition of FITC(10)BSA binding to macrophage was observed even at 10(-9) M conce ntration of specific monovalent ligands tested indicating that these l igands were bound by the putative macrophage receptor with high appare nt affinity. Structural comparisons of the various inhibitors employed , demonstrated that accessible, unconjugated phenyl rings were bound b y the putative receptor with high apparent affinity whereas non-phenyl derivatives were bound with either low apparent affinity or via non-s pecific interactions. Therefore, the fluorescein hapten appeared to ut ilize a receptor with specificity for an essential aromatic amino acid for gaining entry into the endocytic pathway of murine macrophage. Fi nally, the binding of the hapten was enhanced when polyvalent fluoresc ein-derivatized antigens were used as a result of receptor crosslinkag e on the cell surface. (C) 1998 Elsevier Science Ltd. All rights reser ved.