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Open AccessArticle

Granulocyte Colony-Stimulating Factor Does Not Influence Clostridium Perfringens α-Toxin-Induced Myonecrosis in Mice

Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan
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Toxins 2019, 11(9), 509; https://doi.org/10.3390/toxins11090509
Received: 11 July 2019 / Revised: 20 August 2019 / Accepted: 28 August 2019 / Published: 30 August 2019
Clostridium perfringens type A causes gas gangrene characterized by myonecrosis and development of an effective therapy for treating affected patients is of clinical importance. It was recently reported that the expression of granulocyte colony-stimulating factor (G-CSF) is greatly up-regulated by C. perfringens infection. However, the role of G-CSF in C. perfringens-mediated myonecrosis is still unclear. Here, we assessed the destructive changes in C. perfringens-infected skeletal muscles and tested whether inhibition of G-CSF receptor (G-CSFR) signaling or administration of recombinant G-CSF affects the tissue injury. Severe edema, contraction of muscle fiber diameter, and increased plasma creatine kinase activity were observed in mice intramuscularly injected with C. perfringens type A, and the destructive changes were α-toxin-dependent, indicating that infection induces the destruction of skeletal muscle in an α-toxin-dependent manner. G-CSF plays important roles in the protection of tissue against damage and in the regeneration of injured tissue. However, administration of a neutralizing antibody against G-CSFR had no profound impact on the destructive changes to skeletal muscle. Moreover, administration of recombinant human G-CSF, filgrastim, imparted no inhibitory effect against the destructive changes caused by C. perfringens. Together, these results indicate that G-CSF is not beneficial for treating C. perfringens α-toxin-mediated myonecrosis, but highlight the importance of revealing the mechanism by which C. perfringens negates the protective effects of G-CSF in skeletal muscle. View Full-Text
Keywords: Clostridial myonecrosis; phospholipase C; host-pathogen interaction; granulocyte colony-stimulating factor Clostridial myonecrosis; phospholipase C; host-pathogen interaction; granulocyte colony-stimulating factor
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Takehara, M.; Sonobe, Y.; Bandou, H.; Kobayashi, K.; Nagahama, M. Granulocyte Colony-Stimulating Factor Does Not Influence Clostridium Perfringens α-Toxin-Induced Myonecrosis in Mice. Toxins 2019, 11, 509.

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