Specific binding of endocrine transforming growth factor-beta 1 to vascular endothelium.

The presentation of recombinant biologically active 'MI- TGF-.81 via the bloodstream to potential target cells in mice and rats was evaluated by quantitative light and electron microscope radioautography. Specificity was evaluated by in vivo competition with excess unlabeled TGF-81, and in- tegrity of the ligand at the binding site was demonstrated by trichloroacetic acid precipitation after extraction from tissues. The distribution of radiolabel at 2.5, 15, 30, 45, and 60 min after 1"I-TGF-81 injection revealed radiolabel prin- cipally over microvasculature endothelium but at times > 2.5 min over endothelial endocytic components indicative of internalization. Nonspecific binding of 251I-TGF-p1 to the apex of the proximal convoluted tubule of the kidney indi- cated it as the likely site of rapid clearance of TGF-81 from the circulation, while a comparison of the binding of 'MI- TGF-,B1 (endothelial) to that of '"I-TGF-p1 complexed with a2-macroglobulin-methylamine (liver parenchyma) indicated that clearance of TGF-pl complexed a2-macro- globulin was likely via the hepatic at2-macroglobulin recep- tor. The endothelial TGF-.3 receptors uncovered here are likely involved in the local regulatory mechanism of leukocyte and monocyte adhesion and tissue infiltration regulated by endocrine TGF-p1. (J. Clin. Invest 1995.95:2539-2554.) Key words: TGF-fi receptor * systemic TGF-p * microvasculature * inflammation * endoglin In the present study we have used the radioautographic tech- nique to evaluate the distribution of '"I-TGF-/31 -specific bind- ing sites that are accessible to endocrine TGF-f31, and we have defined the vascular endothelium, and especially that of the microvasculature, as a major site of TGF-,61 -specific binding in vivo at 2.5 min after injection. The endothelial binding sites that we observed at this time were saturable and could be distinguished from binding sites related to clearance, i.e., the proximal convoluted tubule of the kidney for uncomplexed Transforming Growth Factor-/31 Binding to Endothelium In Vivo 2539