Antibodies to CD36 (GPIV) inhibit platelet adhesion to subendothelial surfaces under flow conditions.
The membrane glycoprotein CD36 (glycoprotein [GP] IV) has previously been shown to accelerate the initial interaction of platelets with purified type I collagen in both static and flow systems. In the present study, the role of CD36 on platelet interaction with physiologically relevant collagenous surfaces was addressed. Using arterial subendothelium (SE) and endothelial cell extracellular matrix (ECM), studies were performed under flow conditions with annular and parallel-plate perfusion chambers, respectively, at a shear rate of 800 s-1 for 2, 5, and 10 minutes. Perfusates consisted of citrated normal blood samples incubated with Fab fragments of a monospecific polyclonal anti-CD36 antibody or with each of three new anti-CD36 monoclonal antibodies (MoAbs) that inhibit platelet adhesion to purified type I collagen in a static system (131.4, 131.5, and 131.7). Perfusions over SE were also carried out using citrated blood samples from a Naka-negative donor, whose platelets lack CD36. Morphometric evaluation of the perfused samples showed that polyclonal anti-CD36 Fab and the three monoclonal anti-CD36 antibodies inhibited platelet adhesion to the two substrates by 40% after 2 minutes of perfusion and by 30% after 5 minutes (P < .005 on SE and P < .01 on ECM), but at 10 minutes, significant inhibition was seen only on SE with polyclonal anti-CD36 Fab. Similar inhibitions were seen with Naka-negative platelets on SE. These studies demonstrate that CD36 plays a role in the early stages of platelet adhesion to physiologically relevant subendothelial surfaces.
Diaz-Ricart
M
M
Servicio Hemoterapia y Hemostasia, Hospital Clínic i Provincial, Barcelona, Spain.
Tandon
N N
NN
Gómez-Ortiz
G
G
Carretero
M
M
Escolar
G
G
Ordinas
A
A
Jamieson
G A
GA
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018955:CD36 Antigens / Q000276:immunology* / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans; D010477:Perfusion; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology*; D014471:Umbilical Veins
D000911:Antibodies, Monoclonal; D018955:CD36 Antigens