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Blood, 15 August 2001, Vol. 98, No. 4, pp. 1055-1062
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Variable protection of  3-integrin-deficient mice from
thrombosis initiated by different mechanisms
Susan S. Smyth,
Ernane D. Reis,
Heikki Väänänen,
Wen Zhang, and
Barry S. Coller
From the Departments of Medicine, Surgery, and
Biophysics and Physiology, Mount Sinai School of Medicine, New York,
NY.
Platelet integrin  IIb 3 (GPIIb/IIIa) plays a central role in
the initiation of arterial thrombosis, but its contribution to
disseminated microvascular thrombosis is less well defined. Therefore,
wild-type mice (3+/+), 3-integrin-deficient mice
(3 /), and wild-type mice treated with a hamster
monoclonal antibody (1B5) that blocks murine IIb3 function were
tested in models of large-vessel and microvascular thrombosis. In the
large-vessel model, ferric chloride was used to injure the carotid
artery, and the time to thrombosis was measured. In 3+/+
mice, the median time to occlusion was 6.7 minutes, whereas occlusion did not occur in any of the 3/ mice tested
(P < .001). Fab and F(ab')2 fragments of
1B5 increased the median time to occlusion. To initiate systemic
intravascular thrombosis, prothrombotic agents were administered
intravenously, and platelet thrombus formation was monitored by the
decrease in circulating platelet count. Three minutes after the
injection of adenosine diphosphate (ADP), collagen + epinephrine,
or tissue factor, the platelet counts in 3+/+ mice
decreased by 289, 424, and 429 × 103/µL, respectively.
3/ mice and wild-type mice pretreated with 1B5 Fab
(1 mg/kg, IP) were nearly completely protected from the effects of ADP.
In contrast, 3/ mice were only partially protected
from the effects of collagen + epinephrine and minimally protected
from the effects of tissue factor. In all cases, less fibrin became
deposited in the lungs of 3/ mice than in wild-type
mice. These results suggest that though IIb3 plays a
dominant role in large-vessel thrombosis, it plays a variable role in
systemic intravascular thrombosis.
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