Variable protection of beta 3-integrin--deficient mice from thrombosis initiated by different mechanisms |
| |
Authors: | Smyth S S Reis E D Väänänen H Zhang W Coller B S |
| |
Affiliation: | From the Departments of Medicine, Surgery, andBiophysics and Physiology, Mount Sinai School of Medicine, New York,NY. |
| |
Abstract: | Platelet integrin IIb3 (GPIIb/IIIa) plays a central role inthe initiation of arterial thrombosis, but its contribution todisseminated microvascular thrombosis is less well defined. Therefore,wild-type mice (3+/+), 3-integrin-deficient mice(3/), and wild-type mice treated with a hamstermonoclonal antibody (1B5) that blocks murine IIb3 function weretested in models of large-vessel and microvascular thrombosis. In thelarge-vessel model, ferric chloride was used to injure the carotidartery, 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 of1B5 increased the median time to occlusion. To initiate systemicintravascular thrombosis, prothrombotic agents were administeredintravenously, and platelet thrombus formation was monitored by thedecrease in circulating platelet count. Three minutes after theinjection of adenosine diphosphate (ADP), collagen + epinephrine,or tissue factor, the platelet counts in 3+/+ micedecreased 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 protectedfrom the effects of collagen + epinephrine and minimally protectedfrom the effects of tissue factor. In all cases, less fibrin becamedeposited in the lungs of 3/ mice than in wild-typemice. These results suggest that though IIb3 plays adominant role in large-vessel thrombosis, it plays a variable role insystemic intravascular thrombosis. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
| 点击此处可从《Blood》浏览原始摘要信息 |
|
点击此处可从《Blood》下载免费的PDF全文 |
|