Skin wound repair is not altered in the absence of endogenous AnxA1 or AnxA5, but pharmacological concentrations of AnxA4 and AnxA5 inhibit wound hemostasis

Kreft, Sandra, Klatt, Andreas R., Strassburger, Julia, Poschl, Ernst, Flower, R. J., Emig, Sabine, Reutlingsperger, Chris, Brisson, Alain and Brachvogel, Bent (2016) Skin wound repair is not altered in the absence of endogenous AnxA1 or AnxA5, but pharmacological concentrations of AnxA4 and AnxA5 inhibit wound hemostasis. Cells Tissues Organs, 201 (4). pp. 287-298. ISSN 1422-6405

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Abstract

Skin injury induces the cell surface exposure of phosphati- dylserine (PS) on damaged and dying cells to activate coagu- lation and repair processes. Annexins can bind to PS and may modulate the healing response. Here, we determine the rel- evance of annexins for skin wound healing using AnxA1- and AnxA5-deficient mice and recombinant annexins with dis- tinct PS binding properties. Wound inflammation, closure and the formation of granulation tissue were not altered in AnxA1- or AnxA5-deficient mice or after increasing AnxA5 serum concentrations (100 nM) in wild-type mice. Increased serum concentrations (1 μM) of AnxA5 induced massive bleeding, but wound hemostasis was not delayed by AnxA1. Both annexins interact with PS, but only AnxA5 can form 2-dimensional (2D) arrays on the cell surface. The injection of an AnxA5 mutant that binds to PS but lacks the ability of 2D array formation failed to induce bleeding. 2D lattice- forming AnxA4, with high affinity to PS also caused bleeding, while hemostasis was not affected by AnxA8 with low affin- ity or the AnxA8 mutant with medium affinity for PS and the lack of 2D formation. Increased concentrations of AnxA4 and AnxA5 also delayed coagulation pathway activation in vitro. This effect was attenuated for the AnxA5 mutant as well as for AnxA1 and AnxA8. In conclusion, endogenous AnxA1 and AnxA5 are dispensable for wound hemostasis and re- pair, but pharmacologically excessive concentrations of AnxA4 and AnxA5 inhibit hemostasis in skin wounds.

Item Type:	Article
Uncontrolled Keywords:	annexins,blood coagulation,anticoagulant agent,phosphatidylserine,wound healing
Faculty \ School:	Faculty of Science > School of Biological Sciences
UEA Research Groups:	Faculty of Science > Research Groups > Cells and Tissues
Depositing User:	Pure Connector
Date Deposited:	23 May 2016 16:01
Last Modified:	20 Apr 2023 00:01
URI:	https://ueaeprints.uea.ac.uk/id/eprint/59015
DOI:	10.1159/000445106

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