Radhika V, Thennarasu S, Naik N R, Kumar A, Advani S H, Bhisey A N
Cancer Research Institute, Tata Memorial Centre, Parel, Bombay, India.
Am J Hematol. 1996 Jul;52(3):155-64. doi: 10.1002/(SICI)1096-8652(199607)52:3<155::AID-AJH4>3.0.CO;2-S.
Binding of chemoattractant to polymorphonuclear leukocytes (PMNL) triggers a series of events like polymerization of actin and tubulin, orientation of cells, chemotaxis, increase in fluid pinocytosis and phagocytosis, and stimulation of microbicidal pathways which includes lysosomal degranulation and generation of reactive oxygen species. Earlier studies from our laboratory have shown that stimulation of chemotaxis, fluid pinocytosis, and actin polymerization of CML PMNL in response to a synthetic chemotactic peptide formyl-methionyl-leucyl-phenylalanine (fMLP) is significantly lower than that in normal PMNL. It is not known whether this lower response of CML PMNL to fMLP is a global phenomenon involving different chemoattractant receptors or is restricted to the fMLP pathway. We have evaluated chemoattractant induced degranulation process in normal and CML PMNL to fMLP, platelet activating factor (PAF), leukotriene B4 (LTB4), and an analogue of fMLP viz formyl-methionine-1 aminocyclooctane 1 carboxylic acid-phenylalanine-O-methionine (FACC8) using release of lysozyme as a parameter. We find that after stimulation with fMLP and FACC8, the mean percent release of lysozyme was significantly lower in CML PMNL as compared to that in normal cells (P < 0.001). There was no significant difference between the two after stimulation with PAF and LTB4. The results indicate that the fMLP pathway is suppressed in CML granulocytes whereas PAF and LTB4 pathways appear unaltered in these cells. We therefore also studied the kinetics of peptide-receptor interaction with a labelled hexapeptide fNLPNTL which binds to the fMLP receptor. Our results show that the number of fMLP receptors/cell is significantly lower in CML PMNL (P < 0.05) than in normal PMNL, while their affinity constants and dissociation constants were comparable.
趋化因子与多形核白细胞（PMNL）结合会引发一系列事件，如肌动蛋白和微管蛋白聚合、细胞定向、趋化作用、液体胞饮作用和吞噬作用增强，以及刺激包括溶酶体脱颗粒和活性氧生成在内的杀菌途径。我们实验室早期的研究表明，慢性粒细胞白血病（CML）患者的PMNL对合成趋化肽甲酰甲硫氨酰亮氨酰苯丙氨酸（fMLP）的趋化作用、液体胞饮作用及肌动蛋白聚合反应的刺激明显低于正常PMNL。目前尚不清楚CML患者的PMNL对fMLP的这种较低反应是涉及不同趋化因子受体的普遍现象，还是仅限于fMLP途径。我们以溶菌酶释放为参数，评估了正常和CML患者的PMNL对fMLP、血小板活化因子（PAF）、白三烯B4（LTB4）以及fMLP类似物甲酰甲硫氨酸-1-氨基环辛烷-1-羧酸-苯丙氨酸-O-甲硫氨酸（FACC8）的趋化因子诱导的脱颗粒过程。我们发现，用fMLP和FACC8刺激后，CML患者的PMNL中溶菌酶的平均释放百分比明显低于正常细胞（P < 0.001）。用PAF和LTB4刺激后，两者之间无显著差异。结果表明，CML粒细胞中的fMLP途径受到抑制，而PAF和LTB4途径在这些细胞中似乎未改变。因此，我们还研究了与标记的六肽fNLPNTL（其与fMLP受体结合）的肽-受体相互作用动力学。我们的结果表明，CML患者的PMNL中每个细胞的fMLP受体数量明显低于正常PMNL（P < 0.05），而它们的亲和常数和解离常数相当。
