Role of glycoprotein IIa (beta 1 subunit of very late activation antigens)
in platelet functions
S Parmentier, B Catimel, L McGregor, LL Leung and JL McGregor
INSERM U.331, Faculte de Medecine Alexis Carrel, Lyon, France.
Very late activation antigens (VLAs) are glycoproteins (GPs) that play a
major role in platelet adhesion to extracellular matrix. These GPs, members
of the integrin family, are heterodimer complexes with different alpha
subunits noncovalently associated with a common beta 1 subunit known as
GPIIa. GPIa-IIa (also known as VLA2), GPIc-IIa (VLA5), and GPIc*-IIa (VLA6)
are involved, respectively, in platelet adhesion to collagen, fibronectin,
and laminin. At this stage, very little is known about the role of GPIIa in
platelet adhesive functions. In this study, we have generated a monoclonal
antibody (MoAb) (LYP22) directed against GPIIa. Immunoaffinity
chromatography using LYP22 combined with two-dimensional nonreduced-reduced
sodium dodecyl sulfate- polyacrylamide gel electrophoresis shows that the
antibody brings down all VLA subunits. Western blots indicate that the
binding site of LYP22 on GPIIa is disulfide bridge-dependent. The number of
LYP22 binding sites is not increased on stimulation with thrombin and is in
the range of what is observed with another anti-GPIIa MoAb (A-1A5). LYP22
is the first anti-GPIIa MoAb to inhibit aggregation and secretion of washed
platelets stimulated with collagen, thrombin, or arachidonic acid.
Moreover, the lag-phase usually observed on collagen stimulation is
significantly prolonged (by 60 seconds) in the presence of LYP22. This
lag-phase, mediated by LYP22, is also observed in the presence of plasma
proteins and is coupled with a reduced effect on collagen- induced platelet
aggregation. In addition, LYP22 affects the adhesion of resting platelets
to type III collagen, but not to fibronectin, laminin, or type I collagen.
These results strongly indicate that the site on GPIIa, bearing the LYP22
epitope, is an active participant in signal transduction controlling
platelet functions.
Volume 78,
Issue 8,
pp. 2021-2026,
10/15/1991
Copyright © 1991 by The American Society of Hematology
