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© The Rockefeller University Press, 0021-9525/1997//707 $5.00
The Journal of Cell Biology, Volume 138, Number 3, , 1997 707-717

Article

CD36 Mediates the In Vitro Inhibitory Effects of Thrombospondin-1 on Endothelial Cells



David W. Dawson*, S. Frieda A. Pearce§, Ruiqin Zhong{ddagger}, Roy L. Silverstein§, William A. Frazier{ddagger}, and Noël P. Bouck*

* Department of Microbiology-Immunology and Robert H. Lurie Cancer Center, Northwestern University Medical School, Chicago, Illinois 60611; {ddagger} Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110; and § Department of Medicine, Division of Hematology-Oncology, Cornell University Medical College, New York 10021

Thrombospondin-1 (TSP-1) is a naturally occurring inhibitor of angiogenesis that is able to make normal endothelial cells unresponsive to a wide variety of inducers. Here we use both native TSP-1 and small antiangiogenic peptides derived from it to show that this inhibition is mediated by CD36, a transmembrane glycoprotein found on microvascular endothelial cells. Both IgG antibodies against CD36 and glutathione-S-transferase–CD36 fusion proteins that contain the TSP-1 binding site blocked the ability of intact TSP-1 and its active peptides to inhibit the migration of cultured microvascular endothelial cells. In addition, antiangiogenic TSP-1 peptides inhibited the binding of native TSP-1 to solid phase CD36 and its fusion proteins, as well as to CD36-expressing cells. Additional molecules known to bind CD36, including the IgM anti-CD36 antibody SM{emptyset}, oxidized (but not unoxidized) low density lipoprotein, and human collagen 1, mimicked TSP-1 by inhibiting the migration of human microvascular endothelial cells. Transfection of CD36-deficient human umbilical vein endothelial cells with a CD36 expression plasmid caused them to become sensitive to TSP-1 inhibition of their migration and tube formation. This work demonstrates that endothelial CD36, previously thought to be involved only in adhesion and scavenging activities, may be essential for the inhibition of angiogenesis by thrombospondin-1.

Abbreviations used in this paper: BCEC, bovine capillary endothelial cell; bFGF, basic fibroblast growth factor; FP, fusion protein; GST, glutathione-S-transferase; HMVEC, human microvascular endothelial cell; HUVEC, human umbilical vein endothelial cell; IAP, integrin-associated protein; (Ox)LDL, (oxidized) low-density lipoprotein; TSP-1, thrombospondin-1.

Address all correspondence to Noël P. Bouck, Cancer Center, Northwestern University Medical School, 303 East Chicago Ave., Chicago, IL 60611. Tel.: (312) 503-5934. Fax: (312) 908-1372. E-mail: n-bouck{at}nwu.edu


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