Universität zu Köln

Kreft, Sandra, Klatt, Andreas R., Strassburger, Julia, Poschl, Ernst, Flower, Rod J., Eming, Sabine, Reutelingsperger, Chris, Brisson, Alain and Brachvogel, Bent (2015). 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). S. 287 - 299. BASEL: KARGER. ISSN 1422-6421

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Abstract

Skin injury induces the cell surface exposure of phosphatidylserine (PS) on damaged and dying cells to activate coagulation and repair processes. Annexins can bind to PS and may modulate the healing response. Here, we determine the relevance of annexins for skin wound healing using AnxA1- and AnxA5-deficient mice and recombinant annexins with distinct 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 mu M) 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 affinity 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 repair, but pharmacologically excessive concentrations of AnxA4 and AnxA5 inhibit hemostasis in skin wounds. (C) 2016 S. Karger AG, Basel

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kreft, Sandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Klatt, Andreas R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Strassburger, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Poschl, Ernst UNSPECIFIED UNSPECIFIED UNSPECIFIED Flower, Rod J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Eming, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Reutelingsperger, Chris UNSPECIFIED UNSPECIFIED UNSPECIFIED Brisson, Alain UNSPECIFIED UNSPECIFIED UNSPECIFIED Brachvogel, Bent UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-415017
DOI:	10.1159/000445106
Journal or Publication Title:	Cells Tissues Organs
Volume:	201
Number:	4
Page Range:	S. 287 - 299
Date:	2015
Publisher:	KARGER
Place of Publication:	BASEL
ISSN:	1422-6421
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ANNEXIN-V; THROMBOGENIC MECHANISM; BINDING; ANTICOAGULANT; IV Multiple languages Anatomy & Morphology; Cell Biology; Developmental Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41501