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Endotoxin enhances microvascular thrombosis in mouse cremaster venules via a TLR4‐dependent, neutrophil‐independent mechanism
Author(s) -
Rumbaut Rolando E.,
Bellera Ricardo V.,
Randhawa Jaspreet K.,
Shrimpton Corie N.,
Dasgupta Swapan K.,
Dong JingFei,
Burns Alan R.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a699-b
Subject(s) - cremaster muscle , platelet , thrombus , endothelium , platelet activation , intravital microscopy , platelet adhesiveness , thrombosis , microcirculation , p selectin , tlr4 , immunology , ex vivo , medicine , in vivo , chemistry , inflammation , biology , in vitro , biochemistry , platelet aggregation , microbiology and biotechnology
Endotoxemia promotes adhesive interactions between platelets and microvascular endothelium in vivo . We sought to determine whether endotoxin (LPS) modified platelet thrombus formation in mouse cremaster venules, and whether Toll‐like receptor 4 (TLR4) and neutrophils were involved in the response. Intravital videomicroscopy was performed in the cremaster microcirculation of pentobarbital‐anesthetized mice; venular platelet thrombi were induced with a light/dye endothelial injury model. C57BL/6 mice treated with E. coli endotoxin had enhanced rates of venular platelet thrombus formation: the time to microvessel occlusion was reduced by~50% (p < 0.005) compared to saline‐treated animals. Enhanced microvascular thrombosis was evident as early as two hours following LPS administration. LPS had no effect on thrombosis in either of two mouse strains with altered TLR4 signaling (C57BL/10ScNJ or C3H/HeJ), whereas it enhanced thrombosis in the control strains (C57BL/10J and C3H/HeN). LPS also enhanced platelet adhesion to endothelium in the absence of light/dye injury. Platelet adhesion, but not enhanced thrombosis, was inhibited by depletion of circulating neutrophils. LPS failed to enhance platelet aggregation ex vivo , and did not influence platelet P‐selectin expression, a marker of platelet activation. These findings support the notion that endotoxemia promotes platelet thrombus formation independent of neutrophils, and without enhancement of platelet aggregation, via a TLR4‐dependent mechanism.