CD36 MEDIATES THE IN-VITRO INHIBITORY EFFECTS OF THROMBOSPONDIN-1 ON ENDOTHELIAL-CELLS

Thrombospondin-1 (TSP-1) is a naturally occurring inhibitor of angioge nesis that is able to make normal endothelial cells unresponsive to a wide variety of inducers. Here we use both native TSP-1 and small anti angio,oenic peptides derived from it to show that this inhibition is m ediated by CD36, a transmembrane glycoprotein found on microvascular e ndothelial cells, Both IgG antibodies against CD36 and glutathione-S-t ransferase-CD36 fusion proteins that contain the TSP-1 binding site bl ocked the ability of intact TSP-1 and its active peptides to inhibit t he migration of cultured microvascular endothelial cells, In addition, antiangiogenic TSP-1 peptides inhibited the binding of native TSP-1 t o solid phase CD36 and its fusion proteins, as well as to CD36-express ing cells, Additional molecules known to bind CD36, including the IgM anti-CD36 antibody SMO, oxidized (but not unoxidized) low density lipo protein, and human collagen 1, mimicked TSP-1 by inhibiting the migrat ion of human microvascular endothelial cells. Transfection of CD36-def icient human umbilical vein endothelial cells with a CD36 expression p lasmid caused them to become sensitive to TSP-1 inhibition of their mi gration and tube formation. This work demonstrates that endothelial CD 36, previously thought to be involved only in adhesion and scavenging activities, may be essential for the inhibition of angiogenesis by thr ombospondin-1.