Premium
Critical Role of FcR γ‐Chain, LAT, PLCγ2 and Thrombin in Arteriolar Thrombus Formation upon Mild, Laser‐Induced Endothelial Injury In Vivo
Author(s) -
Kalia Neena,
Auger Jocelyn M.,
Atkinson Ben,
Watson Steve P.
Publication year - 2008
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1080/10739680701728822
Subject(s) - gpvi , thrombus , hirudin , thrombin , gene knockout , intravital microscopy , chemistry , knockout mouse , microbiology and biotechnology , platelet activation , pharmacology , platelet , immunology , in vivo , receptor , medicine , biology , biochemistry , gene
Objective : The role of collagen receptor complex GPVI‐FcR γ‐chain, PLCγ2 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 γ‐chain, LAT, PLCγ2 and thrombin. Methods : Thrombi were monitored using intravital microscopy in anesthetized wild‐type and FcR γ‐chain, LAT and PLCγ2 knockout mice. Hirudin (thrombin inhibitor) was administered to wild‐type and FcR γ‐chain knockout mice. Results : Significantly reduced thrombus formation was observed in FcR γ‐chain and PLCγ2 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 γ‐chain knockouts treated with hirudin. Conclusions : GPVI‐FcR γ‐chain, LAT and PLCγ2 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.