Abstract: TH-PO879

The Involvement of p38MAPK in Impaired Neutrophil Bactericidal Activity of Hemodialysis Patients

Session Information

  • Dialysis: Infection
    November 02, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Dialysis

  • 610 Dialysis: Infection

Authors

  • Kamikawa, Yasutaka, Division of Nephrology, Kanazawa University Hospital, Kanazawa, Japan
  • Wada, Takashi, Division of Nephrology, Kanazawa University Hospital, Kanazawa, Japan
  • Sakai, Norihiko, Division of Nephrology, Kanazawa University Hospital, Kanazawa, Japan
  • Shinozaki, Yasuyuki, Division of Nephrology, Kanazawa University Hospital, Kanazawa, Japan
  • Kitajima, Shinji, Division of Nephrology, Kanazawa University Hospital, Kanazawa, Japan
  • Toyama, Tadashi, Division of Nephrology, Kanazawa University Hospital, Kanazawa, Japan
  • Hara, Akinori, Division of Nephrology, Kanazawa University Hospital, Kanazawa, Japan
  • Iwata, Yasunori, Division of Nephrology, Kanazawa University Hospital, Kanazawa, Japan
  • Shimizu, Miho, Division of Nephrology, Kanazawa University Hospital, Kanazawa, Japan
  • Furuichi, Kengo, Division of Nephrology, Kanazawa University Hospital, Kanazawa, Japan
Background

Mortality from infections has been reported to be higher in hemodialysis (HD) patients than that in healthy subjects. Previous studies reported that vascular access was the main route of bacterial infection in HD patients and also pointed that the most common micro-organism were staphylococcus aureus (S. aureus). To protect the host from bacterial infection, neutrophils have been thought to play central roles in the pathogenesis of the infection. This far, the dysfunction of neutrophils against bacterial infection in HD patients was reported. However the precise mechanism of neutrophil dysfunction in HD patients against bacteria remains unclear. In this study, we investigated the impacts of neutrophil inflammatory signaling against bacterial infection in HD patients.

Methods

Comprehensive analyses of intracellular signalings were performed in whole blood of HD patients and hypertensive (HT) patients as control using microarray system. None of patients had diabetes, cardiovascular disease and cancer. 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 S. aureus.

Results

There were no difference at age and nutrition states such as serum albumin levels, cholesterol profile between HD and HT patients. 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.

Conclusion

Impairment of p38MAPK signaling pathway might contribute to the suppression of neutrophil bactericidal activity in HD patients through the less production of ROS.