Targeted disruption of cd39/ATP diphosphohydrolase results in disordered hemostasis and thromboregulation.
CD39, or vascular adenosine triphosphate diphosphohydrolase, has been considered an important inhibitor of platelet activation. Unexpectedly, cd39-deficient mice had prolonged bleeding times with minimally perturbed coagulation parameters. Platelet interactions with injured mesenteric vasculature were considerably reduced in vivo and purified mutant platelets failed to aggregate to standard agonists in vitro. This platelet hypofunction was reversible and associated with purinergic type P2Y1 receptor desensitization. In keeping with deficient vascular protective mechanisms, fibrin deposition was found at multiple organ sites in cd39-deficient mice and in transplanted cardiac grafts. Our data indicate a dual role for adenosine triphosphate diphosphohydrolase in modulating hemostasis and thrombotic reactions.
Enjyoji
K
K
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Sévigny
J
J
Lin
Y
Y
Frenette
P S
PS
Christie
P D
PD
Esch
J S
JS
Imai
M
M
Edelberg
J M
JM
Rayburn
H
H
Lech
M
M
Beeler
D L
DL
Csizmadia
E
E
Wagner
D D
DD
Robson
S C
SC
Rosenberg
R D
RD
D000251:Adenosine Triphosphatases; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001081:Apyrase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001160:Arterioles / Q000473:pathology; D001760:Bleeding Time; D001777:Blood Coagulation; D001792:Blood Platelets / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D005260:Female; D005337:Fibrin / Q000378:metabolism; D017353:Gene Deletion; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D016027:Heart Transplantation / Q000276:immunology / Q000473:pathology; D006487:Hemostasis; D008297:Male; D008643:Mesentery / Q000098:blood supply; D051379:Mice; D018345:Mice, Knockout; D010974:Platelet Aggregation; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000502:physiology; D058472:Receptors, Purinergic P2Y1; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000473:pathology
D015703:Antigens, CD; C546383:P2ry1 protein, mouse; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D005337:Fibrin; D013925:Thromboplastin; D000251:Adenosine Triphosphatases; D001081:Apyrase; C067869:CD39 antigen