THE ROLE OF TUMOR-NECROSIS-FACTOR IN HOST-DEFENSE AGAINST SCRUB TYPHUS RICKETTSIAE .1. INHIBITION OF GROWTH OF RICKETTSIA-TSUTSUGAMUSHI, KARP STRAIN, IN CULTURED MURINE EMBRYONIC-CELLS AND MACROPHAGES BY RECOMBINANT TUMOR-NECROSIS-FACTOR-ALPHA

THE ROLE OF TUMOR-NECROSIS-FACTOR IN HOST-DEFENSE AGAINST SCRUB TYPHUS RICKETTSIAE .1. INHIBITION OF GROWTH OF RICKETTSIA-TSUTSUGAMUSHI, KARP STRAIN, IN CULTURED MURINE EMBRYONIC-CELLS AND MACROPHAGES BY RECOMBINANT TUMOR-NECROSIS-FACTOR-ALPHA
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DOI:
10.1111/j.1348-0421.1994.tb01845.x
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发表时间:
1994-01-01
影响因子:
2.6
通讯作者:
JERRELLS, TR
JERRELLS, TR
中科院分区:
医学4区
文献类型:
--
作者:
GENG, PG;JERRELLS, TR

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在小鼠胚胎细胞系C3 H/10 T1/2克隆8中,重组鼠肿瘤坏死因子-α(TNF-α)在100至10 U/ml的剂量下抑制恙虫病立克次体Karp株的细胞内生长。当腹腔渗出液巨噬细胞或骨髓源性巨噬细胞用作立克次体生长的宿主细胞时,TNF-α的生长抑制作用也很明显。干扰素-γ(IFN-γ),在剂量高达1,000 U/ml时,不影响这种立克次体菌株在小鼠胚胎细胞系中的生长,但正如预期的那样,深刻抑制立克次体在腹腔渗出液巨噬细胞和骨髓源性巨噬细胞中的生长。TNF-α对小鼠胚胎细胞系中立克次体生长的影响不能被IFN-γ重复增强。用TNF-α处理细胞系延迟了立克次体细胞病变效应,但立克次体最终在细胞中生长到高数量并导致细胞死亡。这些发现表明,至少在我们的系统中,R.恙虫病在除巨噬细胞以外的细胞中对IFN-γ介导的抗立克次体作用具有抗性。这项研究的结果支持TNF-α可能抑制立克次体在巨噬细胞以外的细胞中生长的建议。
Recombinant murine tumor necrosis factor-alpha (TNF-alpha) inhibited intracellular growth of Rickettsia tsutsugamushi, Karp strain, in the mouse embryo cell line C3H/10T1/2 clone 8 at doses of 100 to 10 U/ml. The growth inhibitory effect of TNF-alpha was also evident when peritoneal exudate macrophages or bone marrow-derived macrophages were used as the host cell for rickettsial growth. Interferon-gamma (IFN-gamma), at doses up to 1,000 U/ml, did not affect the growth of this strain of rickettsiae in the mouse embryo cell line but, as expected, profoundly inhibited rickettsial growth in peritoneal exudate macrophages and bone marrow-derived macrophages. The effect of TNF-alpha on rickettsial growth in the mouse embryo cell line was not reproducibly enhanced by IFN-gamma. Treatment of the cell line with TNF-alpha delayed rickettsial cytopathic effects, but the rickettsiae ultimately grew to high numbers in the cells and caused cell death. These findings show that, at least in our system, R. tsutsugamushi is resistant to IFN-gamma-mediated antirickettsial effects in cells other than macrophages. The results of this study support the suggestion that TNF-alpha may inhibit rickettsial growth in cells other than macrophages.