Macrophage-Derived Immunoglobulin M Inhibits Inflammatory Responses via Modulating Endoplasmic Reticulum Stress.
Macrophage-Derived Immunoglobulin M Inhibits Inflammatory Responses via Modulating Endoplasmic Reticulum Stress.
复制标题
巨噬细胞源性免疫球蛋白M通过调节内质网应激抑制炎症反应。
作者：
Gong X;Yan H;Ma J;Zhu Z;Zhang S;Xu W;Huang J;Qiu X
免疫球蛋白（IG）是B细胞的特征性标志物，是一种多功能进化保守抗体，对于维持组织稳态和发展对病原体的完全保护性体液应答至关重要。越来越多的证据表明，IG广泛表达于非免疫细胞中，而且不同谱系细胞产生的IG具有不同的生物学功能。最近，据报道单核细胞或巨噬细胞也表达IG。然而，其功能仍不清楚。在本研究中，我们进一步确定了IG，尤其是IG μ重链（IgM）主要在小鼠巨噬细胞中表达。我们还分析了巨噬细胞中IgM的特征，发现巨噬细胞来源的IgM的VHDJH重排显示出限制性和保守的VHDJH模式，这与个体中B细胞表达的IgM的多样性VHDJH重排模式不同。功能研究表明，IgM敲低显著促进巨噬细胞迁移和FAK/Src-Akt轴激活。此外，在LPS刺激下，一些炎性细胞因子如MCP 1和IL-6在IgM敲低后增加。机制研究表明，IgM与结合免疫球蛋白（Bip）相互作用，抑制巨噬细胞的炎症反应和未折叠蛋白反应（UPR）激活。我们的数据阐明了IgM在巨噬细胞中的一种以前未知的功能，解释了其作为Bip的新型调节剂参与内质网应激并进一步调节炎症反应的能力。
Immunoglobulin (Ig), a characteristic marker of B cells, is a multifunctional evolutionary conserved antibody critical for maintaining tissue homeostasis and developing fully protective humoral responses to pathogens. Increasing evidence revealed that Ig is widely expressed in non-immune cells; moreover, Ig produced by different lineages cells plays different biological roles. Recently, it has been reported that monocytes or macrophages also express Ig. However, its function remains unclear. In this study, we further identified that Ig, especially Ig mu heavy chain (IgM), was mainly expressed in mice macrophages. We also analyzed the IgM repertoire characteristic in macrophages and found that the VHDJH rearrangements of macrophage-derived IgM showed a restricted and conservative VHDJH pattern, which differed from the diverse VHDJH rearrangement pattern of the B cell-expressed IgM in an individual. Functional investigation showed that IgM knockdown significantly promoted macrophage migration and FAK/Src-Akt axis activation. Furthermore, some inflammatory cytokines such as MCP1 and IL-6 increased after IgM knockdown under LPS stimulation. A mechanism study revealed that the IgM interacted with binding immunoglobulin protein (Bip) and inhibited inflammatory response and unfolded protein response (UPR) activation in macrophages. Our data elucidate a previously unknown function of IgM in macrophages that explains its ability to act as a novel regulator of Bip to participate in endoplasmic reticulum stress and further regulate the inflammatory response.
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影响因子：
16
作者：
Feige, Matthias J.;Groscurth, Sandra;Marcinowski, Moritz;Shimizu, Yuichiro;Kessler, Horst;Hendershot, Linda M.;Buchner, Johannes
通讯作者：
Buchner, Johannes
影响因子：
10.6
作者：
Busch, Svenja;Talamini, Marina;Fuchs, Tina
通讯作者：
Fuchs, Tina
影响因子：
64.8
作者：
HAAS, IG;WABL, M
通讯作者：
WABL, M
影响因子：
11.4
作者：
Qiu, X.;Sun, X.;Yin, C. C.
通讯作者：
Yin, C. C.
DOI：
10.1083/jcb.200708093
发表时间：
2007-12-17
期刊：
The Journal of cell biology
影响因子：
--
作者：
Owen KA;Pixley FJ;Thomas KS;Vicente-Manzanares M;Ray BJ;Horwitz AF;Parsons JT;Beggs HE;Stanley ER;Bouton AH
通讯作者：
Bouton AH