Nitric oxide- and oxygen-derived free radical generation from control and lipopolysaccharide-treated rat polymorphonuclear leukocyte

被引:30
作者
Sethi, S [1 ]
Sharma, P [1 ]
Dikshit, M [1 ]
机构
[1] Cent Drug Res Inst, Div Pharmacol, Lucknow 226001, Uttar Pradesh, India
来源
NITRIC OXIDE-BIOLOGY AND CHEMISTRY | 2001年 / 5卷 / 05期
关键词
nitric oxide; L-arginine uptake; free radicals; lipopolysaccharide; neutrophils;
D O I
10.1006/niox.2001.0375
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Previous studies from this lab have shown NO-mediated modulation of free radical generation from polymorphonuclear leukocytes (PMNs), following hypoxic-reoxygenation as well as in the normoxic cells. The present study is an attempt to investigate further the regulation of NO and free radical generation in the lipopolysaccharide (LPS)treated PMNs. PMNs were isolated from the rat blood and peritoneal cavity, 4 h after LPS (1 mg/kg, i.p.) treatment. Nitric oxide synthase (NOS) activity and nitrite content were increased in the peripheral and peritoneal PMNs following LPS treatment. An increase in the apparent V-max for L-arginine uptake was also observed in the LPS-treated peripheral PMNs, while peritoneal PMNs exhibited increase in both apparent V-max and affinity for L-arginine. Synthesis of nitrite did not augment after increasing the availability of substrate to control PMNs, however, peripheral and peritoneal PMNs from LPS-treated rats utilized L-arginine more efficiently for nitrite synthesis. NOS activity, L-arginine uptake, and its utilization were maximal in the peritoneal PMNs. Arachidonic acid (AA, 1 x 10(-6) M)-induced free radical generation from PMNs was also enhanced significantly after LPS treatment. Preincubation of PMNs with nitrite elevated the free radical generation and myeloperoxidase (MPO) release. MPO and antioxidant enzyme activity in the PMNs was significantly augmented after LPS treatment. NOS inhibitors, aminoguanidine and 7-nitroindazole, inhibited arachidonic acid-induced free radical generation from LPS treated PMNs. The results obtained thus indicate that augmentation of free radical generation from rat PMNs following LPS treatment appears to be regulated by NO and MPO. (C) 2001 Academic Press.
引用
收藏
页码:482 / 493
页数:12
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