The interaction between C5a and both C5aR and C5L2 receptors is required for production of G-CSF during acute inflammation.
The interaction between C5a and both C5aR and C5L2 receptors is required for production of G-CSF during acute inflammation.
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DOI：
10.1002/eji.201243075
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发表时间：
2013-07
影响因子：
5.4
通讯作者：
Ward, Peter A.
中科院分区：
文献类型：
--
作者：
Bosmann, Markus;Haggadone, Mikel D.;Zetoune, Firas S.;Sarma, J. Vidya;Ward, Peter A.
补体激活产物C5 a是调节炎症反应的关键因素。C5 a和C5 adesArg与它们的受体C5 aR和C5 L2结合，但C5 L2的功能作用仍然存在争议。我们筛选了23种炎症介质的模式，在LPS激活的小鼠腹腔巨噬细胞（PEM）的存在或不存在的重组小鼠C5 a的文化。研究的大多数介质的产生被C5 a抑制，而G-CSF的产生被增强。从PEM的G-CSF基因表达和分泌被C5 a以剂量和时间依赖性方式扩增2-3倍。降解产物C5 adesArg促进较低水平的G-CSF。C5 a对G-CSF的影响与激活PI 3 K/Akt和MEK 1/2信号通路有关。C5 a并不增强来自C5 aR缺陷型或C5 L2缺陷型小鼠的PEM培养物中的G-CSF产生，这表明两种C5 a受体对于介导C5 a在G-CSF产生中的作用是必不可少的。最后，与C57 BL/6 J野生型小鼠相比，C5 aR缺陷或C5 L2缺陷小鼠盲肠结扎穿孔（CLP）后多微生物脓毒症期间血浆中的G-CSF水平显著降低。这些发现阐明了C5 L2受体在急性炎症反应中的功能特征。
The complement activation product, C5a, is a key factor for regulation of inflammatory responses. C5a and C5adesArg bind to their receptors, C5aR and C5L2, but the functional roles of C5L2 remain controversial. We screened the patterns of 23 inflammatory mediators in cultures of LPS-activated mouse peritoneal elicited macrophages (PEMs) in the presence or absence of recombinant mouse C5a. Production of most mediators studied was suppressed by C5a, whereas G-CSF production was enhanced. G-CSF gene expression and secretion from PEMs was amplified 2–3-fold by C5a in a dose and time dependent fashion. The degradation product C5adesArg promoted lower levels of G-CSF. The effects of C5a on G-CSF were associated with activation of PI3K/Akt and MEK1/2 signaling pathways. C5a did not enhance G-CSF production in cultures of PEMs from either C5aR-deficient or C5L2-deficient mice, indicating that both C5a receptors are indispensable for mediating the effects of C5a in production of G-CSF. Finally, G-CSF levels in plasma during polymicrobial sepsis after cecal ligation and puncture (CLP) were substantially lower in C5aR-deficient or C5L2-deficient mice as compared to C57BL/6J wild type mice. These findings elucidate the functional characteristics of the C5L2 receptor during the acute inflammatory response.
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影响因子：
4.8
作者：
Bosmann, Markus;Patel, Vinay R.;Ward, Peter A.
通讯作者：
Ward, Peter A.
影响因子：
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作者：
Bosmann, Markus;Ward, Peter A.
通讯作者：
Ward, Peter A.
影响因子：
4.4
作者：
Huber-Lang, M;Sarma, JV;Ward, PA
通讯作者：
Ward, PA
影响因子：
4.4
作者：
Bosmann, Markus;Haggadone, Mikel D.;Ward, Peter A.
通讯作者：
Ward, Peter A.
影响因子：
4.8
作者：
Cain, SA;Monk, PN
通讯作者：
Monk, PN