Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kasiri, MM; Beer, L; Nemec, L; Gruber, F; Pietkiewicz, S; Haider, T; Simader, EM; Traxler, D; Schweiger, T; Janik, S; Taghavi, S; Gabriel, C; Mildner, M; Ankersmit, HJ.
Dying blood mononuclear cell secretome exerts antimicrobial activity.
Eur J Clin Invest. 2016; 46(10):853-863
Doi: 10.1111/eci.12667
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- Co-Autor*innen der Med Uni Graz
- GABRIEL Christian
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- Abstract:
- 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. 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. 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. 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. © 2016 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.
- Find related publications in this database (using NLM MeSH Indexing)
- Adolescent -
- Adult -
- Animals -
- Anti-Infective Agents - pharmacokinetics
- Antimicrobial Cationic Peptides - metabolism
- Antimicrobial Cationic Peptides - pharmacology
- Apoptosis - radiation effects
- Cell Death -
- Gamma Rays -
- Gram-Negative Bacterial Infections - drug therapy
- Gram-Positive Bacterial Infections - drug therapy
- Humans -
- Leukocytes, Mononuclear - metabolism
- Leukocytes, Mononuclear - physiology
- Male -
- Rats, Sprague-Dawley -
- Young Adult -
- Find related publications in this database (Keywords)
- Antimicrobial peptides
- diabetic foot ulcer
- MNC secretome
- mononuclear cell
- peripheral blood mononuclear cells