Phosphatidylserine Exposure after Vascular Injury-Platelet or Endothelial

Background: Platelets’ membranes are considered the paramount site for the assembly of tenase and prothrombinase complex and are key players in localising coagulation to wound sites. However, the endothelium is also known to express phosphatidylserine (PS) and support the binding of recombinant FVa/FXa even beyond the site of injury. It thus remain unclear, what cell type play the preeminent role in the cellular control of coagulation after vascular injury. Approach: To address this question, we utilised a model of haemostasis (full thickness 1mm excisional skin wounds) as well as tissues after injury in laser and ferric chloride models of thrombosis. Damage to the endothelium was assessed by the combined methods of picrosirius red staining, immunofluorescence and electron microscopy. Using multiphoton microscopy, we then compared the spatial distribution of PS on platelets and the endothelium. Results: Platelets and detectable PS significantly co-localised compared with similar analysis of endothelial cell and exposed PS on wounded carotids arteries which was not significant. Point injury by laser induced restricted damage of the endothelium which was associated with limited platelets recruitment. In consistence with platelets’ response after FeCl3 injury, platelets exposed most of the PS detected at the wound edge where skin vessels were transected in our haemostasis model (Correlation Coeff. 0.78±0.12 vs 0.35±0.23). Conclusions: We surmised that data from the different models support a paradigm of graded haemostatic response to vascular injury, in which full platelets’ response is limited to wound sites exposing the sub-endothelial matrix. Running Title: Platelets Localise Predominant Phosphatidylserine.