Induction of nitrite/nitrate synthesis in murine macrophages by BCG infection, lymphokines, or interferon-gamma.
Induction of nitrite/nitrate synthesis in murine macrophages by BCG infection, lymphokines, or interferon-gamma.
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DOI：
10.4049/jimmunol.139.2.518
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发表时间：
1987-07
影响因子：
4.4
通讯作者：
D. Stuehr;M. Marletta
中科院分区：
文献类型：
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作者：
D. Stuehr;M. Marletta
用C_3 H/He和C_3 H/HeJ小鼠巨噬细胞研究了BCG感染激活后，或经T细胞衍生的淋巴因子（LK）或重组鼠干扰素-γ（IFN-γ）、细菌脂多糖（LPS）和热灭活卡介苗（hk BCG）体外处理后，巨噬细胞合成亚硝酸盐和硝酸盐的情况。从BCG感染的供体中分离出的脾脏和腹腔巨噬细胞产生硝酸盐，继续在培养中合成亚硝酸盐和硝酸盐。体外LPS处理（25或50微克/毫升）还增加了这种亚硝酸盐/硝酸盐的合成。来自用LK处理的未感染的C3 H/HeJ小鼠的巯基乙酸盐诱导的巨噬细胞也产生亚硝酸盐/硝酸盐，并且同时LPS（0.1至50微克/ml）处理导致合成增强。重组IFN-γ还刺激C3 H/He和CeH/HeJ巨噬细胞的亚硝酸盐/硝酸盐合成，如LPS（仅C3 H/He）和hk BCG。当与LPS或HK BCG同时给予时，IFN-γ增强C3 H/He和C3 H/HeJ巨噬细胞亚硝酸盐/硝酸盐的合成，超过单独用LPS或HK BCG处理的巨噬细胞产生的亚硝酸盐/硝酸盐。在体外活化的大环内酯在参与亚硝酸盐/硝酸盐合成之前表现出4至12小时的滞后时间，然后以线性速率进行36至42小时。每日培养基更新没有改变合成动力学，但增加了亚硝酸盐/硝酸盐的总量。硝酸盐和亚硝酸盐在培养条件下是稳定的，并且当添加时不影响额外的巨噬细胞合成。两者合计，这些结果表明，T细胞淋巴因子和IFN-γ是强大的巨噬细胞亚硝酸盐/硝酸盐合成的调节剂在BCG感染和体外，亚硝酸盐/硝酸盐合成似乎是引发和完全激活的巨噬细胞群体的共同属性。
Macrophage synthesis of nitrite and nitrate after activation by BCG infection or by treatment in vitro with both T cell-derived (lymphokines (LK) or recombinant murine interferon-gamma (IFN-gamma] and bacterial (lipopolysaccharide (LPS) and heat-killed bacillus Calmette-Guerin (hk BCG] agents was studied by using macrophages from C3H/He and C3H/HeJ mice. Spleen and peritoneal macrophages isolated from BCG-infected donors that were producing nitrate continued to synthesize nitrite and nitrate in culture. LPS treatment in vitro (25 or 50 micrograms/ml) additionally increased this nitrite/nitrate synthesis. Thioglycolate-elicited macrophages from non-infected C3H/HeJ mice treated with LK also produced nitrite/nitrate, and concurrent LPS (0.1 to 50 micrograms/ml) treatment resulted in enhanced synthesis. Recombinant IFN-gamma also stimulated nitrite/nitrate synthesis by C3H/He and CeH/HeJ macrophages as did LPS (C3H/He only) and hk BCG. When given concurrently with either LPS or hk BCG, IFN-gamma enhanced C3H/He and C3H/HeJ macrophage nitrite/nitrate synthesis over that produced by macrophages treated with either LPS or hk BCG alone. Macrophages activated in vitro exhibited a 4 to 12 hr lag time before engaging in nitrite/nitrate synthesis, which then proceeded for 36 to 42 hr at linear rates. Daily medium renewal did not alter the synthesis kinetics but increased the total amount of nitrite/nitrate produced. Nitrate and nitrite were stable under the conditions of culture and when added did not influence additional macrophage synthesis. Taken together, these results indicate that T cell lymphokines and IFN-gamma are powerful modulators of macrophage nitrite/nitrate synthesis during BCG infection and in vitro, and nitrite/nitrate synthesis appears to be common property of both primed and fully activated macrophage populations.