Dying blood mononuclear cell secretome exerts antimicrobial activity. (26th September 2016)

• Record Type: Journal Article
• Authors: Kasiri, Mohammad Mahdi; Beer, Lucian; Nemec, Lucas; Gruber, Florian; Pietkiewicz, Sabine; Haider, Thomas; Simader, Elisabeth Maria; Traxler, Denise; Schweiger, Thomas; Janik, Stefan; Taghavi, Shahrokh; Gabriel, Christian; Mildner, Michael; Ankersmit, Hendrik Jan
• Is Part Of: European journal of clinical investigation. Volume 46:Number 10(2016:Oct.)
• Page Start: 853
• Page End: 863
• Publication Date: 2016-09-26
• Subjects: Antimicrobial peptides -- diabetic foot ulcer -- MNC secretome -- mononuclear cell -- peripheral blood mononuclear cells; Pathology -- Periodicals; Medical research -- Periodicals; 616.075
• DOI: 10.1111/eci.12667
• Languages: English
• ISSNs: 0014-2972

Abstract

Abstract: Background: Several activities are attributed to antimicrobial peptides (AMPs), including bacterial killing, leucocyte recruitment and angiogenesis. Despite promises of advanced cellular therapies for treatment of diabetic foot ulcer, it is currently accepted that paracrine factors rather than cellular components are causative for the observed effects. Whether AMPs are present in the mononuclear cell (MNC) secretome (MNC‐sec) of white blood cells that are beneficial in experimental wound healing is not known. Materials and methods: Antimicrobial activity of the secretomes of nonirradiated (MNC‐sec) and γ‐irradiated MNCs (MNC‐sec rad) was analysed by microdilution assay. AMPs were determined by quantitative real‐time PCR (RT‐PCR) and enzyme‐linked immunosorbent assay (ELISA). Whether human MNC‐sec rad causes AMP secretion in vivo was examined in an experimental rat model. Image flow cytometry was used to determine the type of cell death induced in MNCs after exposure to γ‐radiation. Results: The antimicrobial activity assay revealed a bactericidal activity of MNC‐sec rad and to a lesser degree also of MNC‐sec. Image flow cytometry showed that γ‐irradiation of MNCs induced early apoptosis followed mainly by necroptosis. RT‐PCR and ELISA revealed a high abundance of different AMPs in the secretome of MNCs. In addition, human MNC‐sec elicited an increase in de novo endogenous AMP production in rats in vivo . Conclusion: We provide evidence that the secretome of MNCs has direct and indirect positive effects on the immune defence system, including augmentation of antibacterial properties. Our data further suggest that necroptosis could play a key role for the release of paracrine factors and the therapeutic action of MNC‐sec rad.