Language
English
Publication Date
11-1-2022
Journal
Microcirculation
DOI
10.1111/micc.12782
PMID
36056797
PMCID
PMC9720896
PubMedCentral® Posted Date
12-5-2022
PubMedCentral® Full Text Version
Author MSS
Abstract
Objective: Extracellular histones are known mediators of platelet activation, inflammation, and thrombosis. Von Willebrand Factor (vWF) and Toll-like receptor 4 (TLR4) have been implicated in pro-inflammatory and prothrombotic histone responses. The objective of this study was to assess the role of vWF and TLR4 on histone-induced platelet adhesion in vivo.
Methods: Intravital microscopy of the mouse cremaster microcirculation, in the presence of extracellular histones or saline control, was conducted in wild-type, vWF-deficient, and TLR4-deficient mice to assess histone-mediated platelet adhesion. Platelet counts following extracellular histone exposure were conducted. Platelets were isolated from vWF-deficient mice and littermates to assess the role of vWF on histone-induced platelet aggregation.
Results: Histones promoted platelet adhesion to cremaster venules in vivo in wild-type animals, as well as in TLR4-deficient mice to a comparable degree. Histones did not lead to increased platelet adhesion in vWF-deficient mice, in contrast to littermate controls. In all genotypes, histones resulted in thrombocytopenia. Histone-induced platelet aggregation ex vivo was similar in vWF-deficient mice and littermate controls.
Conclusions: Histone-induced platelet adhesion to microvessels in vivo is vWF-dependent and TLR4-independent. Platelet-derived vWF was not necessary for histone-induced platelet aggregation ex vivo. These data are consistent with the notion that endothelial vWF, rather than platelet vWF, mediates histone-induced platelet adhesion in vivo.
Keywords
Animals, Mice, von Willebrand Factor, Histones, Toll-Like Receptor 4, Venules, Blood Platelets, von Willebrand Factor, vWF, histones, platelets, TLR4, Toll-like Receptor 4, cremaster, microvessel, aggregation, adherence
Published Open-Access
yes
Recommended Citation
Courson, Justin A; Lam, Fong W; Langlois, Kimberly W; et al., "Histone-Stimulated Platelet Adhesion to Mouse Cremaster Venules In Vivo Is Dependent on Von Willebrand Factor" (2022). Faculty and Staff Publications. 4037.
https://digitalcommons.library.tmc.edu/baylor_docs/4037