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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.

Dying blood mononuclear cell secretome exerts antimicrobial activity