MAMMALIAN NITRATE BIOSYNTHESIS - MOUSE MACROPHAGES PRODUCE NITRITE AND NITRATE IN RESPONSE TO ESCHERICHIA-COLI LIPOPOLYSACCHARIDE
MAMMALIAN NITRATE BIOSYNTHESIS - MOUSE MACROPHAGES PRODUCE NITRITE AND NITRATE IN RESPONSE TO ESCHERICHIA-COLI LIPOPOLYSACCHARIDE
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DOI：
10.1073/pnas.82.22.7738
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发表时间：
1985-01-01
影响因子：
11.1
通讯作者：
MARLETTA, MA
中科院分区：
文献类型：
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作者：
STUEHR, DJ;MARLETTA, MA
在LPS敏感的C3 H/He和LPS抵抗的C3 H/HeJ小鼠中研究了大肠杆菌脂多糖（LPS）诱导的硝酸盐生物合成。腹膜内注射15 μ g LPS导致C3 H/He菌株中血液硝酸盐浓度暂时增加5至6倍。尿液中排出的硝酸盐水平也增加了。相反，在C3 H/HeJ菌株中用高达175 μ g的LPS注射没有观察到增加。此外，当与LPS（10 μ g/ml）一起培养时，巯基乙酸盐引发的来自C3 H/He而不是来自C3 H/HeJ小鼠的腹膜巨噬细胞产生亚硝酸盐（60%）和硝酸盐（40%）。T淋巴细胞添加/耗竭实验表明T细胞的存在增强了这种反应。然而，LPS并没有导致亚硝酸盐或硝酸盐的生产在培养的脾淋巴细胞从任一菌株。在裸鼠和CBA/N小鼠中也观察到LPS诱导的硝酸盐合成，表明体内应答既不需要功能性T淋巴细胞也不需要LPS应答性B淋巴细胞。这与体外结果一致，表明单独的巨噬细胞具有活性。牛分枝杆菌感染C3 H/He和C3 H/HeJ小鼠导致在两种菌株的感染过程中硝酸盐产量大幅增加，表明T淋巴细胞介导的巨噬细胞活化是硝酸盐生物合成的有力刺激。亚硝酸盐的合成是重要的，因为它可以直接参与亚硝胺的内源性形成，也可能参与细胞毒性化学的某些方面。
Escherichia coli lipopolysaccharide (LPS)-induced nitrate biosynthesis was studied in LPS-sensitive C3H/He and LPS-resistant C3H/HeJ mice. Intraperitoneal injection of 15 .mu.g of LPS led to a temporary 5- to 6-fold increase in blood nitrate concentration in the C3H/He strain. Levels of nitrate excreted in the urine were also increased. In contrast, no increase was observed in the C3H/HeJ strain with LPS injections up to 175 .mu.g. Furthermore, thioglycolate-elicited peritoneal macrophages from C3H/He, but not from C3H/HeJ mice, produced nitrite (60%) and nitrate (40%) when cultured with LPS (10 .mu.g/ml). T-lymphocyte addition/depletion experiments showed the presence of T cells enhanced this response. However, LPS did not cause nitrite or nitrate production in cultures of spleen lymphocytes from either strain. LPS-induced nitrate synthesis was also observed with nude mice and CBA/N mice, indicating that neither functional T lymphocytes nor LPS-responsive B lymphocytes were required for the response in vivo. This was consistent with the in vitro results showing macrophages alone were competent. Mycobacterium bovis infection of C3H/He and C3H/HeJ mice resulted in a large increase in nitrate production over the course of the infection for both strains, suggesting T-lymphocyte-mediated activation of macrophages as a potent stimulus for nitrate biosynthesis. The synthesis of nitrite is significant in that it can directly participate in the endogenous formation of nitrosamines and may also be involved in some aspect of the chemistry of cytotoxicity.