Journal
MICROCIRCULATION
Volume 15, Issue 4, Pages 325-335Publisher
WILEY
DOI: 10.1080/10739680701728822
Keywords
platelets; collagen; signalling molecules; thrombin; intravital
Categories
Funding
- MRC [G0300102] Funding Source: UKRI
- British Heart Foundation Funding Source: Medline
- Medical Research Council [G0300102] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
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Objective: The role of collagen receptor complex GPVI-FcR gamma-chain, PLC gamma 2 and LAT in laser-induced thrombosis is unclear. Controversy surrounds whether collagen is exposed in this model or whether thrombosis is dependent on thrombin. This study hypothesized that collagen exposure plays a critical role in thrombus formation in this model, which was tested by investigating contributions of FcR gamma-chain, LAT, PLC gamma 2 and thrombin. Methods: Thrombi were monitored using intravital microscopy in anesthetized wild-type and FcR gamma-chain, LAT and PLC gamma 2 knockout mice. Hirudin (thrombin inhibitor) was administered to wild-type and FcR gamma-chain knockout mice. Results: Significantly reduced thrombus formation was observed in FcR gamma-chain and PLC gamma 2 knockouts with a greater decrease observed in LAT knockouts. Dramatic reduction was observed in wild-types treated with hirudin, with abolished thrombus formation only observed in FcR gamma-chain knockouts treated with hirudin. Conclusions: GPVI-FcR gamma-chain, LAT and PLC gamma 2 are essential for thrombus generation and stability in this laser-induced model of injury. More importantly, a greater role for LAT was identified, which may reflect a role for it downstream of a second matrix protein receptor. However, inhibition of platelet activation by matrix proteins and thrombin generation are both required to maximally prevent thrombus formation.
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