Platelet hyperactivity in TNFSF14/LIGHT knockout mouse model of impaired healing

Sandeep Dhall, Zubair A. Karim, Fadi T. Khasawneh, Manuela Martins-Green

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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 of TNFSF14/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 for TNFSF14/LIGHT during wound healing. Conclusion: The absence of TNFSF14/LIGHT from 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.

Original languageEnglish (US)
Pages (from-to)421-431
Number of pages11
JournalAdvances in Wound Care
Volume5
Issue number10
DOIs
StatePublished - Oct 1 2016
Externally publishedYes

Keywords

  • P-selectin, integrin α IIb β 3
  • phosphatidylserine
  • platelet aggregation
  • thrombosis and occlusion

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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