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人源抗菌肽LL-37可直接激活肥大细胞,使其合成促炎介质并产生迁移反应。

Human-derived cathelicidin LL-37 directly activates mast cells to proinflammatory mediator synthesis and migratory response.

作者信息

Bąbolewska Edyta, Brzezińska-Błaszczyk Ewa

机构信息

Department of Experimental Immunology, Medical University of Łódź, Pomorska 251, 92-213 Łódź, Poland.

Department of Experimental Immunology, Medical University of Łódź, Pomorska 251, 92-213 Łódź, Poland.

出版信息

Cell Immunol. 2015 Feb;293(2):67-73. doi: 10.1016/j.cellimm.2014.12.006. Epub 2015 Jan 3.

DOI:10.1016/j.cellimm.2014.12.006
PMID:25577339
Abstract

Cathelicidins, a family of antimicrobial peptides, are well known for their role in host defense, particularly against bacteria. Apart from direct killing of microbes through the membrane disruption, cathelicidins can also exert immunomodulatory effects on cells involved in inflammatory processes. Considering the important role of mast cells in inflammation, the aim of this study was to determine whether LL-37, human-derived cathelicidin, can induce mast cell activation. We have observed that LL-37 directly stimulates mast cell to degranulation and production of some proinflammatory cytokines, but fails to induce cysteinyl leukotriene generation and release. We have also documented that LL-37 acts as a strong mast cell chemoattractant. In intracellular signaling in mast cells activated by LL-37 participates PLC/A2 and, in part, MAPKs, and PI3K. In conclusion, our results indicate that cathelicidins may enhance antibacterial inflammatory response via attracting mast cell to pathogen entry site and via induction of mast cell-derived mediator release.

摘要

cathelicidin抗菌肽家族以其在宿主防御尤其是抗细菌防御中的作用而闻名。除了通过破坏细胞膜直接杀死微生物外,cathelicidin抗菌肽还可对参与炎症过程的细胞发挥免疫调节作用。鉴于肥大细胞在炎症中的重要作用,本研究旨在确定人源cathelicidin抗菌肽LL-37是否能诱导肥大细胞活化。我们观察到LL-37可直接刺激肥大细胞脱颗粒并产生一些促炎细胞因子,但不能诱导半胱氨酰白三烯的生成和释放。我们还证明LL-37是一种强大的肥大细胞趋化因子。在LL-37激活的肥大细胞的细胞内信号传导中,PLC/A2以及部分MAPKs和PI3K参与其中。总之,我们的结果表明,cathelicidin抗菌肽可能通过将肥大细胞吸引到病原体进入部位以及诱导肥大细胞衍生介质的释放来增强抗菌炎症反应。

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