Inhibition of platelet functions by a monoclonal antibody (LYP20) directed against a granule membrane glycoprotein (GMP-140/PADGEM).
Granule membrane protein (GMP-140), also known as platelet activation-dependent granule-external membrane (PAD-GEM) is an integral membrane glycoprotein that is expressed on the platelet surface following degranulation. GMP-140, also expressed by endothelial cells, is part of a new family of cell adhesion molecules (selectins) related to the endothelial leukocyte adhesion molecule (ELAM-1) and to the lymphocyte homing receptors in humans (Leu-8/TQ1) and in mouse (gp90MEL-14). The role of GMP-140 in platelet functions remains to be elucidated. In this study, a monoclonal antibody, LYP20, was raised against GMP-140. LYP20, directed against a disulphide bridge-dependent epitope, significantly binds to thrombin-stimulated platelets (12,200 +/- 1,184 bound molecules/platelet, kd = 5.0 +/- 0.61 nmol/L) compared with controls (2,400 +/- 266 molecules/platelet, kd = 2.3 +/- 0.54 nmol/L) and inhibits collagen or thrombin-induced aggregation of washed platelets or platelets in platelet-rich plasma. In addition, LYP20 inhibits rosetting of thrombin-activated platelets to U937 cells. These results strongly suggest that GMP-140 plays an important role in platelet aggregation and platelet interaction with other blood cells.
Parmentier
S
S
INSERM U.331, Faculté de Médecine Alexis Carrel, Lyon, France.
McGregor
L
L
Catimel
B
B
Leung
L L
LL
McGregor
J L
JL
D000911:Antibodies, Monoclonal; D001792:Blood Platelets / Q000502:physiology*; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008970:Molecular Weight; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D012397:Rosette Formation
D000911:Antibodies, Monoclonal; D010980:Platelet Membrane Glycoproteins