Dobos G J, Traynor-Kaplan A E, Ward D, Schollmeyer P J
Department of Medicine, University of California, San Diego 92103.
Clin Investig. 1994 May;72(5):353-7. doi: 10.1007/BF00252827.
We studied the effect of C5a pretreatment on phosphatidyl-inositol-4,5-bisphosphate (PIP2) hydrolysis and on the increase in peak and resting cytosolic calcium levels induced by C5a (0.1 and 10 nM) and/or N-formyl hexapeptide (FLPEP; 10 nM) in neutrophils isolated from patients with end-stage renal failure (ESRF) and those from healthy controls. We also investigated superoxide anion production under the same conditions using the fluorescent para-hydroxyphenylacetic acid assay. The hydrolysis of PIP2 induced by C5a or FLPEP alone was similar in neutrophils from patients with ESRF and in control cells. Likewise, pretreatment of patients' neutrophils with C5a prior to FLPEP did not affect hydrolysis or the increase in cytosolic calcium concentration as shown previously for control neutrophils. Resting calcium levels in both ESRF and control neutrophils, however, were significantly increased after priming with low C5a concentrations. After priming with low C5a, prior to FLPEP, there was also a significant increase in superoxide production. This increase was significantly lower in cells from uremic patients than in those from healthy controls. Our data suggest that priming-induced superoxide production in neutrophils is reduced in patients with ESRF.
我们研究了C5a预处理对磷脂酰肌醇-4,5-二磷酸（PIP2）水解的影响，以及对终末期肾衰竭（ESRF）患者和健康对照者分离出的中性粒细胞中由C5a（0.1和10 nM）和/或N-甲酰六肽（FLPEP；10 nM）诱导的峰值和静息胞质钙水平升高的影响。我们还使用荧光对羟基苯乙酸测定法在相同条件下研究了超氧阴离子的产生。单独的C5a或FLPEP诱导的PIP2水解在ESRF患者的中性粒细胞和对照细胞中相似。同样，如先前对对照中性粒细胞所示，在FLPEP之前用C5a预处理患者的中性粒细胞不会影响水解或胞质钙浓度的升高。然而，用低浓度C5a启动后，ESRF和对照中性粒细胞的静息钙水平均显著升高。在用低浓度C5a启动后，在FLPEP之前，超氧产生也显著增加。尿毒症患者细胞中的这种增加明显低于健康对照者的细胞。我们的数据表明，ESRF患者中性粒细胞中启动诱导的超氧产生减少。
