Lin Chien-Sheng, Wann Joseph G, Hsiao Cheng-Wen, Tai Deborah W, Chen Jin-Shuen, Hsu Yung-Ho, Huang Huei-Chen, Chao Chung-Faye
Institute of Biology and Anatomy, National Defense Medical Center, PO Box 90048-502, Taipei, Taiwan, Republic of China.
Nephrol Dial Transplant. 2008 May;23(5):1642-9. doi: 10.1093/ndt/gfm852. Epub 2007 Dec 8.
We have demonstrated that uraemic neutrophils that exhibit a low intracellular pH (pHi) display enhanced phagocytosis. However, the underlying cellular mechanism is unclear.
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.
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.
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.
我们已经证明，细胞内pH值（pHi）较低的尿毒症中性粒细胞表现出增强的吞噬作用。然而，其潜在的细胞机制尚不清楚。
我们使用了三组透析前血液透析（HD）患者（A组、B组和C组）以及年龄和性别匹配的健康个体的中性粒细胞来测定pHi、吞噬作用以及CD11b、CD18、CD14和Toll样受体（TLR）-2和TLR-4的表达。患者根据连续三个月的透析前血浆碳酸氢盐浓度（P(HCO3)）和pH值进行分类；A组、B组和C组的透析前P(HCO3)分别恒定为≤21、21 - 26和≥26 mmol/L（mEq/L）。我们还研究了代谢性酸中毒的纠正以及针对CD11b/CD18的单克隆抗体（mAb）对A组中性粒细胞的影响。此外，我们在体外研究了细胞内酸化对尿毒症中性粒细胞的影响。
我们观察到，与B组和C组相比，A组的中性粒细胞吞噬作用和CD11b/CD18的表达显著增加。此外，我们的体外研究表明，针对CD11b/CD18的mAb部分阻断了A组中性粒细胞吞噬作用的增强。而且，尿毒症中性粒细胞的pHi与吞噬作用以及CD11b/CD18的表达呈负相关。
与pHi正常或较高的中性粒细胞相比，P(HCO3)较低的HD患者中性粒细胞的pHi较低，这反过来增加了CD11b/CD18的表达。尿毒症中性粒细胞上CD11b/CD18表达的增加可能有助于pHi介导的吞噬作用。
