Nakaseko C, Asai T, Wakita H, Oh H, Saito Y
Second Department of Internal Medicine, Chiba University, School of Medicine, Japan.
Br J Haematol. 1996 Dec;95(3):482-8. doi: 10.1111/j.1365-2141.1996.tb08992.x.
Myelodysplastic syndromes (MDS) are clonal haematological disorders and MDS neutrophils have various abnormal functions which cause an increased risk of infective mortality. We examined luminol-dependent chemiluminescence and cytoplasmic Ca2+ increase in order to characterize the mechanisms of a signalling defect in MDS neutrophil respiratory burst. In MDS patients, chemiluminescence stimulated with N-formyl-L-methionyl-L-leucil-L-phenylalanine (FMLP) and calcium ionophore A23187 was defective (17.2 +/- 13.7 v 44.3 +/- 16.6, P = 0.001; 42.2 +/- 21.3 v 82.0 +/- 23.6, P < 0.05, respectively), but phorbol 12-myristate 13-acetate (PMA) chemiluminescence was normal (73.4 +/- 26.9 v 79.5 +/- 23.8, P = 0.52). There were no statistical significances in cytoplasmic Ca2+ increase stimulated with FMLP and recombinant human interleukin-8 (rhIL-8) compared with controls (251.1 +/- 104.3 v 272.7 +/- 41.2, P = 0.295; 238.6 +/- 65.0 v 253.9 +/- 38.3, P = 0.567, respectively). Flow cytometric analysis of MDS neutrophils disclosed that most MDS patients showed normal neutrophil cytoplasmic Ca2+ response to FMLP and rhIL-8. However, two patients with refractory anaemia with excess of blasts displayed a significant decrease of both chemiluminescence and cytoplasmic Ca2+ response to FMLP, and they also displayed low expression of FMLP receptor. These data suggest that most MDS patients have low FMLP chemiluminescence which is not due to a defect in the FMLP receptor. It is proposed that defective FMLP chemiluminescence in MDS results from a putative defect in protein kinase C- and Ca(2+)-independent cell-signalling mechanisms. Only a small group of patients have numerical or structural defects in the FMLP receptor, causing significant decrease of neutrophil respiratory burst.
骨髓增生异常综合征（MDS）是克隆性血液系统疾病，MDS中性粒细胞具有多种异常功能，这会导致感染性死亡风险增加。我们检测了鲁米诺依赖性化学发光和细胞质Ca2+增加情况，以表征MDS中性粒细胞呼吸爆发信号缺陷的机制。在MDS患者中，用N-甲酰-L-甲硫氨酰-L-亮氨酰-L-苯丙氨酸（FMLP）和钙离子载体A23187刺激的化学发光存在缺陷（分别为17.2±13.7对44.3±16.6，P = 0.001；42.2±21.3对82.0±23.6，P < 0.05），但佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）化学发光正常（73.4±26.9对79.5±23.8，P = 0.52）。与对照组相比，FMLP和重组人白细胞介素-8（rhIL-8）刺激引起的细胞质Ca2+增加无统计学意义（分别为251.1±104.3对272.7±41.2，P = 0.295；238.6±65.0对253.9±38.3，P = 0.567）。对MDS中性粒细胞的流式细胞术分析显示，大多数MDS患者对FMLP和rhIL-8的中性粒细胞细胞质Ca2+反应正常。然而，两名伴有过多原始细胞的难治性贫血患者对FMLP的化学发光和细胞质Ca2+反应均显著降低，并且他们还表现出FMLP受体低表达。这些数据表明，大多数MDS患者的FMLP化学发光较低，这并非由于FMLP受体缺陷所致。有人提出，MDS中FMLP化学发光缺陷是由蛋白激酶C和Ca(2+)非依赖性细胞信号机制中的假定缺陷引起的。只有一小部分患者的FMLP受体存在数量或结构缺陷，并导致中性粒细胞呼吸爆发显著降低。
