Involvement of p38MAPK in Impaired Neutrophil Bactericidal Activity of Hemodialysis Patients |
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| Authors: | Yasutaka Kamikawa Norihiko Sakai Taito Miyake Akihiro Sagara Yasuyuki Shinozaki Shinji Kitajima Tadashi Toyama Akinori Hara Yasunori Iwata Miho Shimizu Kengo Furuichi Ryu Imamura Takashi Suda Shuichi Kaneko Takashi Wada |
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| Affiliation: | 1. Division of Nephrology, Kanazawa University Hospital, Kanazawa, Japan;2. Division of Blood Purification, Kanazawa University Hospital, Kanazawa, Japan;3. Division of Tumor Dynamics and Regulation, Kanazawa University, Kanazawa, Japan;4. Division of Immunology and Molecular Biology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan;5. Department of System Biology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan;6. Department of Nephrology and Laboratory Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan |
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| Abstract: | Mortality from infections has been reported to be higher in hemodialysis (HD) patients. Although dysfunction of neutrophils against bacterial infection was reported in HD patients, the precise mechanism remains to be clarified. We therefore examined the impacts of neutrophil inflammatory signaling on bactericidal activity in HD patients. Comprehensive analyses of intracellular signalings were performed in whole blood of HD patients and control using a microarray system. To confirm the contribution of the signaling to bactericidal activity in neutrophils, we examined the phosphorylation, bacterial killing function, reactive oxygen species (ROS) production, and myeloperoxidase (MPO) release in neutrophils against Staphylococcus aureus. RNA microarray analysis showed the suppression of p38 mitogen activated protein kinase (MAPK) signaling in HD patients. Neutrophils in HD patients showed the impairment of bactericidal activity against S. aureus compared to healthy subjects. Phosphorylation rate of p38MAPK of neutrophils in response to S. aureus was lower in HD patients than healthy subjects. The levels of ROS produced by neutrophils after co‐culture with S. aureus were lower in HD patients, on the other hand, there was no difference of MPO release between HD patients and healthy subjects. A selective pharmacological inhibitor of p38MAPK suppressed bacterial killing function as well as ROS production in neutrophils of healthy subjects. Impairment of p38MAPK signaling pathway might contribute to the suppression of neutrophil bactericidal activity in HD patients through less production of ROS. |
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| Keywords: | Dialysis Infection Neutrophils p38MAPK Reactive oxidative species |
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