The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor.

The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor.
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巨噬细胞是巨噬细胞迁移抑制因子的重要且以前未被认可的来源。

DOI:
10.1084/jem.179.6.1895
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发表时间:
1994-06-01
影响因子:
15.3
通讯作者:
Bucala, Richard
Bucala, Richard
中科院分区:
医学1区
文献类型:
--
作者:
Calandra, Thierry;Bernhagen, Juergen;Mitchell, Robert A.;Bucala, Richard

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25年来,巨噬细胞移动抑制因子(MIF)一直被认为是T淋巴细胞活化的产物。我们最近鉴定了人MIF的小鼠同源物是一种由脑下垂体分泌的蛋白质,对内毒素注射做出反应。在这些研究过程中,我们还在内毒素治疗、T细胞缺陷(Nude)和脑垂体切除小鼠的急性血清中检测到MIF,这表明还有更多的细胞类型产生MIF。在此,我们报道单核/巨噬细胞系的细胞是体内和体外MIF的重要来源。我们观察到在静息的、未受刺激的细胞中,预先形成的MIF蛋白和MIF mRNA的水平都很高。在小鼠巨噬细胞RAW 264.7中,低至10pg/ml的脂多糖可诱导巨噬细胞产生巨噬细胞因子,在1 ng/ml时达到峰值,而在1微克/毫升的脂多糖浓度下则不能被检测到。在RAW 264.7巨噬细胞中,肿瘤坏死因子-α和干扰素-γ也能诱导巨噬细胞分泌肿瘤坏死因子-α,但不能被白介素1-β或6诱导。巨噬细胞在体内既是MIF的重要来源,也是MIF的重要靶点。炎症刺激激活了中枢(垂体)和外周(巨噬细胞)来源的MIF,进一步证明了这种细胞因子在全身对组织侵袭的反应中所起的关键作用。
For over 25 years, the cytokine known as macrophage migration inhibitory factor (MIF) has been considered to be a product of activated T lymphocytes. We recently identified the murine homolog of human MIF as a protein secreted by the pituitary in response to endotoxin administration. In the course of these studies, we also detected MIF in acute sera obtained from endotoxin-treated, T cell- deficient (nude), and hypophysectomized mice, suggesting that still more cell types produce MIF. Here, we report that cells of the monocyte/macrophage lineage are an important source of MIF in vitro and in vivo. We observed high levels of both preformed MIF protein and MIF mRNA in resting, nonstimulated cells. In the murine macrophage cell line RAW 264.7, MIF secretion was induced by as little as 10 pg/ml of lipopolysaccharide (LPS), peaked at 1 ng/ml, and was undetectable at LPS concentrations > 1 microgram/ml. A similar stimulation profile was observed in LPS-treated peritoneal macrophages; however, higher LPS concentrations were necessary to induce peak MIF production unless cells had been preincubated with interferon gamma (IFN-gamma). In RAW 264.7 macrophages, MIF secretion also was induced by tumor necrosis factor alpha (TNF-alpha) and IFN-gamma, but not by interleukins 1 beta or 6. Of note, MIF-stimulated macrophages were observed to secrete bioactive TNF-alpha. Although previously overlooked, the macrophage is both an important source and an important target of MIF in vivo. The activation of both central (pituitary) and peripheral (macrophage) sources of MIF production by inflammatory stimuli provides further evidence for the critical role of this cytokine in the systemic response to tissue invasion.
DOI: 10.1084/jem.167.2.598
发表时间: 1988-02-01
期刊: The Journal of experimental medicine
影响因子: --
作者:
McInnes A;Rennick DM
通讯作者: Rennick DM
DOI: 10.1378/chest.99.1.169
发表时间: 1991-01-01
期刊: CHEST
影响因子: 9.6
作者:
DANNER, RL;ELIN, RJ;PARILLO, JE
通讯作者: PARILLO, JE
DOI: 10.1073/pnas.56.1.72
发表时间: 1966-01-01
影响因子: 11.1
作者:
DAVID, JR
通讯作者: DAVID, JR
DOI: 10.1056/nejm198806093182301
发表时间: 1988-06-09
影响因子: 158.5
作者:
MICHIE, HR;MANOGUE, KR;WILMORE, DW
通讯作者: WILMORE, DW
DOI: 10.1126/science.2821621
发表时间: 1987-10-23
期刊: SCIENCE
影响因子: 56.9
作者:
SAPOLSKY, R;RIVIER, C;VALE, W
通讯作者: VALE, W