Differential expression of antimicrobial peptides in margins of chronic wounds Stefanie Dressel 1 *, Ju ¨ rgen Harder 1 *, Jesko Cordes 1 , Maike Wittersheim 1 , Ulf Meyer-Hoffert 1 , Cord Sunderko ¨ tter 2 * and Regine Gla ¨ ser 1 * 1 Clinical Research Unit at the Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Germany; 2 Department of Dermatology, University of Mu ¨nster, Mu ¨nster, Germany Correspondence: Cord Sunderko ¨tter, Department of Dermatology, University of Mu ¨nster, Von Esmarch Str. 58 48149 Mu ¨nster, Germany, Tel.: 49-251-83-57481, Fax: 49-251-83-57481, e-mail: Cord.Sunderkoetter@ukmuenster.de *These authors contributed equally to this study. Accepted for publication 27 October 2009 Abstract: Skin wounds usually heal without major infections, although the loss of the mechanical epithelial barrier exposes the tissue to various bacteria. One reason may be the expression of antimicrobial peptides (AMP) of which some [human b- defensins (hBD) and LL-37] were recently shown to support additionally certain steps of wound healing. There are no studies which have compared expression patterns of different classes of AMP in chronic wounds. The aim of our study was therefore to analyse the expression profile of hBD-2, hBD-3, LL-37, psoriasin and RNase 7 by immunohistochemistry from defined wound margins of chronic venous ulcers. We detected a strong induction of psoriasin and hBD-2 in chronic wounds in comparison with healthy skin. Except for stratum corneum, no expression of RNase 7 and LL-37 was detected in the epidermis while expression of hBD-3 was heterogeneous. Bacterial swabs identified Staphylococcus aureus and additional bacterial populations, but no association between colonization and AMP expression was found. The differential expression of AMP is noteworthy considering the high bacterial load of chronic ulcers. Clinically, supplementation of AMP with the capability to enhance wound healing besides restricting bacterial overgrowth could present a physiological support for treatment of disturbed wound healing. Key words: antimicrobial peptides – chronic wound – S. aureus – skin infection Please cite this paper as: Differential expression of antimicrobial peptides in margins of chronic wounds. Experimental Dermatology 2010; 19: 628–632. Introduction It is an intriguing experience that most skin wounds heal without major complications, although the loss of the mechanical epithelial barrier exposes the tissue to a high number of bacteria. The major reason for this phenomenon is apparently a very efficient innate immune response which in the skin encompasses the expression of antimicro- bial peptides (AMP). Most of them are released by kerati- nocytes and some by recruited leucocytes (1,2). In addition to their direct antimicrobial effect, AMP contribute consid- erably to other mechanisms in infection and inflammation, such as recruiting leucocytes and activating the adaptive immune response (1,2). Some of them have lately emerged as factors which sup- port processes of wound healing: human b-defensins-1–4 induce proliferation and migration of keratinocytes (3), whereas LL-37 promotes migration of HaCaT keratinocytes (4) and angiogenesis (5), a mandatory ingredient of wound healing. Correspondingly, gene transfer of human b-defen- sin-3 (hBD-3) to infected diabetic porcine wounds has resulted in faster wound closure (6). Furthermore, human neutrophilic peptides (HNP) were shown to induce colla- gen synthesis and also to promote keratinocyte prolifera- tion (7). Other AMP such as psoriasin (S100A7) (8–10) or RNase 7 (11,12) have not been shown to induce processes in tis- sue repair or have not been investigated yet in the context of tissue repair. Because of their possibly distinct functions in wounds, the expression pattern of AMP is relevant in the patho- physiology of wound healing. Several studies have addressed the appearance of individual AMP in acute wounds which in contrast to chronic wounds do not show impaired wound healing. LL-37 (hCAP18) was demon- strated to be highly expressed after surgical wounding (13) Abbreviations: AMP, antimicrobial protein(s); hBD, human beta- defensin(s); IHC, immunohistochemistry; PMN, polymorphonuclear neutrophils; DOI:10.1111/j.1600-0625.2009.01030.x www.blackwellpublishing.com/EXD Original Article 628 ª 2009 John Wiley & Sons A/S, Experimental Dermatology, 19, 628–632