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Platelet GPVI and CLEC-2 in skin wound healing
closure, but not during the inflammatory phase (day 1- 3).43 This is due to a decrease in M2 macrophages,43 sup- porting our observation that a reduction in wound macrophages, particularly M1 phenotype, in the early phase does not negatively affect wound closure but may contribute to the reduction in scar formation.43 The alter- ation in M2 macrophages was not observed in DKO mice although the previous dermatitis model has reported an increase number of M2 phenotypes in GPVI-deficient mice,16 suggesting other contributing factors for macrophage polarization during skin wound healing.6
The increased risk of wound contamination is a con- cern in the context of intra-tissue bleeding and reduced wound leukocytes. However, it has recently been shown that rapid formation of a fibrin film over the surface of the wound is protective against bacterial infection.44 This process might also reduce the need for leukocyte infiltra- tion to kill microbes. Moreover, a previous study has reported that a 2-fold increase in wound neutrophils is driven by Staphylococcus aureus infection.45 Whether the beneficial potential of targeting GPVI and CLEC-2 might modulate the risk of wound infection requires further investigation.
In conclusion, we show that deletion of platelet GPVI
and CLEC-2 facilitates cutaneous wound repair through a local and temporal vascular leakage leading to increased fibrin(ogen) deposition and reduced leukocyte infiltra- tion. Thus, impaired vascular integrity due to the loss of GPVI and CLEC-2 is beneficial to wound repair. This con- trasts with results in coagulation-deficient mice, with dif- ferences explained by altered formation of fibrin and most likely alteration in immune cell trafficking. A short- er duration of healing lowers the risk of complications (e.g. infection) and the cost of caring for the wound.46 Based on our study, targeting CLEC-2 and GPVI at the wound site together with optimal wound care (e.g. asep- tic dressing) might represent a new pathway to promote healing and reduce scar formation.
Acknowledgments
The authors would like to thank the BMSU at the University of Birmingham for technical support in animal experiments and the Technology Hub for imaging assistance.
Funding
This work was supported by the Ministry of Sciences and Technology of Thailand and the British Heart Foundation (RG/13/18/30563). SPW holds a BHF Chair (CH03/003).
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