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Dying blood mononuclear cell secretome exerts antimicrobial activity
Author(s) -
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
Publication year - 2016
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/eci.12667
Subject(s) - flow cytometry , peripheral blood mononuclear cell , in vivo , antimicrobial , immune system , angiogenesis , ex vivo , microbiology and biotechnology , antimicrobial peptides , cytokine , apoptosis , secretion , in vitro , biology , chemistry , pharmacology , immunology , cancer research , biochemistry
Background Several activities are attributed to antimicrobial peptides ( AMP s), 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 AMP s 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 MNC s ( MNC ‐sec rad) was analysed by microdilution assay. AMP s 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 MNC s 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 MNC s induced early apoptosis followed mainly by necroptosis. RT ‐ PCR and ELISA revealed a high abundance of different AMP s in the secretome of MNC s. 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 MNC s 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.