Histone‐stimulated platelet adhesion to mouse cremaster venules in vivo is dependent on von Willebrand factor. (22nd September 2022)

• Record Type: Journal Article
• Authors: Courson, Justin A.; Lam, Fong W.; Langlois, Kimberly W.; Rumbaut, Rolando E.
• Is Part Of: Microcirculation. Volume 29:Number 8(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-09-22
• Subjects: adherence -- aggregation -- cremaster -- histones -- microvessel -- platelets -- TLR4 -- toll‐like receptor 4 -- von Willebrand factor -- vWF; Biological transport -- Periodicals; Microcirculation -- Physiology -- Periodicals; 612.135
• DOI: 10.1111/micc.12782
• Languages: English
• ISSNs: 1073-9688

Abstract

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.