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* Department of Microbiology-Immunology and Robert H. Lurie Cancer Center, Northwestern University Medical School,
Chicago, Illinois 60611; 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
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
, 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.
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