Khalfi F, Gressier B, Brunet C, Dine T, Luyckx M, Cazin M, Cazin J C
Laboratoire de Pharmacologie, Pharmacocinétique Clinique, Faculté des Sciences, Pharmaceutiques et Biologiques, Lille, France.
Cell Mol Biol (Noisy-le-grand). 1996 Dec;42(8):1211-8.
Some proteases (particularly elastase) and metabolites of very reactive oxygen species (superoxide anion, hydrogen peroxide, hypochlorous acid and hydroxyl radicals) are generated by polymorphonuclear neutrophils (PMNs) during inflammatory disorders. Divalent cations, especially calcium (Ca2+) play an important regulatory role in the different PMNs functions. The aim of this study is to determine the role of extracellular calcium during the liberation of elastase and of reactive oxygen species production by human PMNs. Consequently, in order to stimulate PMNs, phorbolmyristate acetate (PMA), formyl-methionyl-leucyl-phenylalanine (fMLP) and opsonized zymosan (OZ) have been used. PMNs stimulated by OZ did not release elastase to reverse the PMA and fMLP systems. The production of elastase by PMNs stimulated by PMA to reverse the fMLP system is independent from the extracellular calcium, between 0.0 and 1.5 mM. With various higher concentrations of calcium, varying from 1.5 to 4.0 mM, the release of elastase by PMNs stimulated by PMA is extracellular calcium-dependent to reverse the fMLP system. The superoxide anion (O2-) generated by PMNs activated by fMLP is dependent from the extracellular calcium in the medium, whereas O2- production by PMA or OZ stimulated neutrophils was extracellular calcium-independent. These observations suggest that an influx of calcium may play an important role in the production of elastase and in the capacity of PMNs stimulated by fMLP to produce O2- to reverse the PMA and OZ systems.
在炎症性疾病期间,多形核中性粒细胞(PMN)会产生一些蛋白酶(特别是弹性蛋白酶)以及高活性氧物质的代谢产物(超氧阴离子、过氧化氢、次氯酸和羟基自由基)。二价阳离子,尤其是钙(Ca2+)在PMN的不同功能中发挥着重要的调节作用。本研究的目的是确定细胞外钙在人PMN释放弹性蛋白酶和产生活性氧物质过程中的作用。因此,为了刺激PMN,使用了佛波酯肉豆蔻酸乙酸酯(PMA)、甲酰甲硫氨酰亮氨酰苯丙氨酸(fMLP)和调理酵母聚糖(OZ)。受OZ刺激的PMN不会释放弹性蛋白酶来逆转PMA和fMLP系统。受PMA刺激以逆转fMLP系统的PMN产生弹性蛋白酶与细胞外钙无关,细胞外钙浓度在0.0至1.5 mM之间。当钙浓度更高,在1.5至4.0 mM之间变化时,受PMA刺激的PMN释放弹性蛋白酶以逆转fMLP系统是依赖细胞外钙的。由fMLP激活的PMN产生的超氧阴离子(O2-)依赖于培养基中的细胞外钙,而由PMA或OZ刺激的中性粒细胞产生O2-则不依赖细胞外钙。这些观察结果表明,钙的内流可能在弹性蛋白酶的产生以及受fMLP刺激的PMN产生O2-以逆转PMA和OZ系统的能力中发挥重要作用。