title: Platelet Hyperactivity inTNFSF14/LIGHTKnockout Mouse Model of Impaired Healing.
abstract: Objective:Impaired and chronic wounds occur due to defects in one or more of the overlapping stages of healing. However, problems related to the vascular system are critical for nonhealing, and chronic wounds in humans often show the presence of fibrin cuffs/clots. We hypothesized that these clots are due to alterations in platelet function; hence, we have investigated whether alterations in platelet function are present during impaired healing.Approach:Platelets were subjected to different agonists to determine the rate of aggregation and evaluate the molecules involved in adhesion and aggregation that could lead to faster thrombosis and potentially contribute to impaired wound healing.Results:We show that wounding ofTNFSF14/LIGHT-/-mice, which have impaired healing, leads to an enhanced response in platelet aggregation and a faster time to blood vessel occlusion (thrombosis). In addition, after wounding, platelets from these mice have increased levels of P-selectin, integrin αIIbβ3, and phosphatidylserine, molecules that contribute to platelet adhesion. They also have more extensive open canalicular system than platelets of control mice, suggesting increased surface area for interactions upon activation.Innovation:These results show a novel function forTNFSF14/LIGHTduring wound healing.Conclusion:The absence ofTNFSF14/LIGHTfrom the cell surface of platelets causes rapid platelet aggregation and thrombus formation that may contribute to impaired healing by reducing the ability of the blood vessels to transport nutrients and oxygen and other molecules needed for proper healing.
authors: Department of Cell Biology and Neuroscience, University of California Riverside , Riverside, California.
authors: Sandeep
authors: S
authors: Dhall
authors: Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences , Pomona, California.
authors: Zubair A
authors: ZA
authors: Karim
authors: Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences , Pomona, California.
authors: Fadi T
authors: FT
authors: Khasawneh
authors: Department of Cell Biology and Neuroscience, University of California Riverside , Riverside, California.
authors: Manuela
authors: M
authors: Martins-Green
keywords: P-selectin; fibrin cuffs; integrin α IIb β 3; phosphatidylserine; platelet aggregation; thrombosis and occlusion