CD36 mediates the In vitro inhibitory effects of thrombospondin-1 on endothelial cells. J Cell Biol 1997 Aug 11;138(3):707-17
Date
08/11/1997Pubmed ID
9245797Pubmed Central ID
PMC2141641DOI
10.1083/jcb.138.3.707Scopus ID
2-s2.0-0030833817 (requires institutional sign-in at Scopus site) 567 CitationsAbstract
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, 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.
Author List
Dawson DW, Pearce SF, Zhong R, Silverstein RL, Frazier WA, Bouck NPAuthor
Roy L. Silverstein MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
CD36 Antigens
Cattle
Cell Movement
Cells, Cultured
Endothelium, Vascular
Humans
Ligands
Membrane Glycoproteins
Molecular Sequence Data
Neovascularization, Physiologic
Peptide Fragments
Recombinant Fusion Proteins
Thrombospondins
Transfection