SPECIFIC BINDING OF ENDOCRINE TRANSFORMING GROWTH-FACTOR-BETA-1 TO VASCULAR ENDOTHELIUM

The presentation of recombinant biologically active I-125-TGF-beta 1 v ia the bloodstream to potential target cells in mice and rats was eval uated by quantitative light and electron microscope radioautography, S pecificity was evaluated by in vivo competition with excess unlabeled TGF-beta 1, and integrity of the ligand at the binding site was demons trated by trichloroacetic acid precipitation after extraction from tis sues, The distribution of radiolabel at 2.5, 15, 30, 45, and 60 min af ter I-125-TGF-beta 1 injection revealed radiolabel principally over mi crovasculature endothelium but at times > 2.5 min over endothelial end ocytic components indicative of internalization. Nonspecific binding o f I-125-TGF-beta 1 to the apex of the proximal convoluted tubule of th e kidney indicated it as the likely site of rapid clearance of TGF-bet a 1 from the circulation, while a comparison of the binding of I-125-T GF-beta 1 (endothelial) to that of I-125-TGF-beta 1 complexed with alp ha(2)-macroglobulin-methylamine (liver parenchyma) indicated that clea rance of TGF-beta 1 complexed alpha 2-macroglobulin was likely via the hepatic alpha 2-macroglobulin receptor. The endothelial TGF-beta rece ptors uncovered here are likely involved in the local regulatory mecha nism of leukocyte and monocyte adhesion and tissue infiltration regula ted by endocrine TGF-beta 1.