Endorepellin, the C-terminal angiostatic module of perlecan, enhances collagen-platelet responses via the alpha2beta1-integrin receptor.
Endorepellin, a C-terminal fragment of the vascular basement membrane proteoglycan perlecan, inhibits angiogenesis via the alpha2beta1-integrin receptor. Because this integrin is also implicated in platelet-collagen responses and because endorepellin or its fragments are generated in response to injury and inflammation, we hypothesized that endorepellin could also affect platelet biology. We discovered that endorepellin supported alpha2beta1-dependent platelet adhesion, without appreciably activating or aggregating platelets. Notably, endorepellin enhanced collagen-evoked responses in platelets, in a src kinase-dependent fashion, and enhanced the collagen-inhibitory effect of an alpha2beta1-integrin function-blocking antibody. Collectively, these results suggest that endorepellin/alpha2beta1-integrin interaction and effects are specific and dependent on cell type, differ from those emanated by exposure to collagen, and may be due to cellular differences in alpha2beta1-integrin activation/ligand affinity state. These studies also suggest a heretofore unrecognized role for angiostatic basement membrane fragments in platelet biology.
Bix
Gregory
G
Department of Pathology, Anatomy and Cell Biology, Kimmel Cancer Center, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.
Iozzo
Rex A
RA
Woodall
Ben
B
Burrows
Michelle
M
McQuillan
Angela
A
Campbell
Shelly
S
Fields
Gregg B
GB
Iozzo
Renato V
RV
D043165:Angiostatic Proteins / Q000378:metabolism* / Q000494:pharmacology; D000906:Antibodies / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003094:Collagen / Q000378:metabolism* / Q000494:pharmacology; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D038982:Integrin alpha2beta1 / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology
D043165:Angiostatic Proteins; D000906:Antibodies; D019812:Heparan Sulfate Proteoglycans; D038982:Integrin alpha2beta1; D010446:Peptide Fragments; C071927:perlecan; D003094:Collagen