ANTIMICROBIAL PROTEINS OF MURINE MACROPHAGES

ANTIMICROBIAL PROTEINS OF MURINE MACROPHAGES
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DOI:
10.1128/iai.61.7.3038-3046.1993
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发表时间:
1993-07-01
影响因子:
3.1
通讯作者:
LEHRER, RI
LEHRER, RI
中科院分区:
医学2区
文献类型:
--
作者:
HIEMSTRA, PS;EISENHAUER, PB;LEHRER, RI

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从γ干扰素激活的鼠巨噬细胞系RAW 264.7的细胞中纯化了三种鼠杀微生物蛋白(MUMP)。类似的蛋白质也存在于非活化的RAW264.7细胞中,在小鼠巨噬细胞系J774A.1的细胞中,以及在居民和活化的小鼠腹腔巨噬细胞中。MUMP-1、MUMP-2和MUMP-3在体外杀死鼠伤寒沙门氏菌、土氏大肠杆菌、金黄色葡萄球菌、单核细胞增生李斯特菌、偶发分枝杆菌和新型隐球菌。MUMP-1类似于Hl组蛋白,但很不寻常,因为它的N末端残基(丝氨酸)没有被N乙酰化。虽然MUMP-2的N端封闭,其高赖氨酸/精氨酸比和其与H1组蛋白抗体的反应性表明,它也属于H1组蛋白家族。MUMP-3与组蛋白H2 B在30个氨基末端残基中的30个相同。虽然组蛋白的抗菌特性已经被认识了几十年,这是第一个证据表明,这些蛋白质可能赋予非氧化性抗菌潜力的巨噬细胞的溶酶体装置。注意到其他MUMP,包括一些具有更有限的抗菌谱的MUMP和γ干扰素刺激后似乎在RAW 264.7细胞中诱导的MUMP,但仍有待表征。
Three murine microbicidal proteins (MUMPs) were purified from cells of the murine macrophage cell line RAW264.7 that had been activated by gamma interferon. Similar proteins were also present in nonactivated RAW264.7 cells, in cells of the murine macrophage cell line J774A.1, and in resident and activated murine peritoneal macrophages. MUMP-1, MUMP-2, and MUMP-3 killed Salmonella typhimurium, Escherchia coli, Staphylococcus aureus, Listeria monocytogenes, Mycobacterium fortuitum, and Cryptococcus neoformans in vitro. MUMP-1 resembled an Hl histone but was unusual because its N-terminal residue (serine) was not N acetylated. Although MUMP-2 was N terminally blocked, its high lysine/arginine ratio and its reactivity with an antibody to H1 histones suggested that it also belonged to the H1 histone family. MUMP-3 was identical to histone H2B in 30 of 30 amino-terminal residues. Although the antimicrobial properties of histones have been recognized for decades, this is the first evidence that such proteins may endow the lysosomal apparatus of macrophages with nonoxidative antimicrobial potential. Other MUMPs, including some with a more restricted antimicrobial spectrum and one that appeared to be induced in RAW264.7 cells after gamma interferon stimulation, were noted but remain to be characterized.