Intracellular acidification enhances neutrophil phagocytosis in chronic haemodialysis patients: possible role of CD11b/CD18.
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(P(HCO3)) and pH values; Groups A, B and C had a constant pre-dialysis P(HCO3) 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 P(HCO3) 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.
Lin
Chien-Sheng
CS
Institute of Biology and Anatomy, National Defense Medical Center, PO Box 90048-502, Taipei, Taiwan, Republic of China.
Wann
Joseph G
JG
Hsiao
Cheng-Wen
CW
Tai
Deborah W
DW
Chen
Jin-Shuen
JS
Hsu
Yung-Ho
YH
Huang
Huei-Chen
HC
Chao
Chung-Faye
CF
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001639:Bicarbonates / Q000097:blood; D039481:CD11b Antigen / Q000097:blood*; D018821:CD18 Antigens / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism*; D010587:Phagocytosis / Q000276:immunology* / Q000502:physiology*; D006435:Renal Dialysis / Q000009:adverse effects*; D015398:Signal Transduction; D014511:Uremia / Q000097:blood / Q000276:immunology / Q000628:therapy
D000911:Antibodies, Monoclonal; D001639:Bicarbonates; D039481:CD11b Antigen; D018821:CD18 Antigens