NDT Advance Access originally published online on December 8, 2007
Nephrology Dialysis Transplantation 2008 23(5):1642-1649; doi:10.1093/ndt/gfm852
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intracellular acidification enhances neutrophil phagocytosis in chronic haemodialysis patients: possible role of CD11b/CD18
1 Graduate Institute of Medical Sciences, National Defense Medical Center 2 Department of Emergency & Critical Care Medicine, Cheng Hsin Rehabilitation Medical Center 3 Department of Physiology, College of Medicine, National Taiwan University 4 Division of Colorectal Surgery, Department of Surgery, Tri-Service General Hospital 5 Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Medical University-Wan Fang Hospital 6 Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital 7 Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Wan Fang Hospital 8 Division of Nephrology, Department of Internal Medicine, Cheng Hsin Rehabilitation Medical Center 9 Department of Biology and Anatomy, National Defense Medical Center
Correspondence and offprint requests to: Chao Chung-Faye, Institute of Biology and Anatomy, National Defense Medical Center, PO Box 90048-502, Taipei, Taiwan, Republic of China. Tel.: +886-2-28264400 ext 6588; Fax: +886-2-28264400; E-mail: spteng1008{at}yahoo.com.tw
 |
Abstract |
|---|
Background. We have demonstrated that uraemic neutrophils that exhibit a low intracellular pH (pHi) display enhanced phagocytosis. However, the underlying cellular mechanism is unclear.
Methods. We used neutrophils from three groups of haemodialysis (HD) patients before dialysis (Groups A, B and C) and also from age- and sex-matched healthy individuals to determine pHi, phagocytosis and expression of CD11b, CD18, CD14 and toll-like receptors (TLR)-2 and TLR-4. The patients were categorized based on three consecutive monthly pre-dialysis plasma bicarbonate concentrations(PHCO3) and pH values; Groups A, B and C had a constant pre-dialysis PHCO3 of 
21, 21–26 and 
26 mmol/L (mEq/L), respectively. We also studied the effects induced by the correction of metabolic acidosis and monoclonal antibodies (mAbs) against CD11b/CD18 on neutrophils in Group A. Furthermore, we investigated the effect of intracellular acidification on uraemic neutrophils ex vivo.
Results. We observed that the neutrophils in Group A exhibited significantly increased phagocytosis and expression of CD11b/CD18 compared with those in Groups B and C. Additionally, our ex vivo studies demonstrated that the mAbs against CD11b/CD18 partially blocked the enhancement of neutrophil phagocytosis in Group A. Moreover, the pHi of uraemic neutrophils is inversely correlated with phagocytosis and expression of CD11b/CD18.
Conclusions. HD patients with a low PHCO3 exhibited low neutrophil pHi that in turn increased the expression of CD11b/CD18 compared with neutrophils with a normal or high pHi. This increased expression of CD11b/CD18 on the uraemic neutrophils may contribute to the pHi-mediated phagocytosis.
Keywords: CD11b/CD18; haemodialysis; intracellular pH; neutrophil; phagocytosis
Received for publication: 30. 4.07
Accepted in revised form: 6.11.07