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肥大细胞与细菌之间的联系:细胞因子的抗菌防御、功能和调节。

Link between mast cells and bacteria: Antimicrobial defense, function and regulation by cytokines.

机构信息

Immunology Division, Postgraduate Medical School, University of Chieti-Pescara, Chieti, Italy.

Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.

出版信息

Med Hypotheses. 2017 Sep;106:10-14. doi: 10.1016/j.mehy.2017.06.018. Epub 2017 Jun 29.

Abstract

Bacteria and their products, such as LPS, act on mast cells (MCs) to induce the secretion of multiple cytokines, including IL-1, TNF, IL-18 and IL-33, which can be dosed in the site of infected tissues. Antigen-binding IgE cross-links FcεRI on mast cells involves the generation and activation of PKCδ, ERK, tyrosine kinases (Syk and Lyn) and mitogen-activated protein kinases (MAPKs), inducing the release of chemical mediators which provoke inflammation and hypersensitive reaction. Other stimuli, including, cytokines, neuropeptides, chemical and physical activators, can also act on MCs to release a plethora of inflammatory compounds. Activated MCs produce a broad spectrum of inflammatory cytokines, chemokines, lipid compounds and vasoactive amines, all involved in immune response. By producing TNF, MCs have an antibacterial defense and a protective function; while pathogenic bacteria and their products, such as LPS, have an inflammatory response through MC activation. LPS binding TLR4 produce MC generation IL-1 family members, and chemokines, which may recruit inflammatory cells at the infection site; whereas in Kit mice, where MCs are genetically absent, the inflammatory effect is not present. We report for the first time a link between MCs and bacteria emphasizing the mediation of inflammatory cytokines/chemokines. We can conclude that mast cells fight bacteria, and their immune response is perfectly integrated in the immune network. We hope that the understanding of microbial and mast cell interaction leads to more efficient therapeutic development in relation to microbial resistance.

摘要

细菌及其产物,如 LPS,作用于肥大细胞(MCs)诱导多种细胞因子的分泌,包括 IL-1、TNF、IL-18 和 IL-33,这些细胞因子可以在感染组织部位给药。抗原结合 IgE 交联 FcεRI 于肥大细胞涉及 PKCδ、ERK、酪氨酸激酶(Syk 和 Lyn)和丝裂原激活蛋白激酶(MAPKs)的产生和激活,诱导化学介质的释放,引发炎症和超敏反应。其他刺激物,包括细胞因子、神经肽、化学和物理激活剂,也可以作用于 MCs 释放大量炎症化合物。活化的 MCs 产生广泛的炎症细胞因子、趋化因子、脂质化合物和血管活性胺,所有这些都参与免疫反应。MCs 通过产生 TNF 具有抗菌防御和保护功能;而致病性细菌及其产物,如 LPS,通过 MC 激活产生炎症反应。LPS 与 TLR4 结合产生 MC 生成的 IL-1 家族成员和趋化因子,这些趋化因子可能在感染部位募集炎症细胞;而在 Kit 小鼠中,MCs 是遗传缺失的,炎症反应不存在。我们首次报道了 MCs 与细菌之间的联系,强调了炎症细胞因子/趋化因子的介导作用。我们可以得出结论,肥大细胞对抗细菌,它们的免疫反应完美地整合在免疫网络中。我们希望对微生物和肥大细胞相互作用的理解能导致与微生物耐药性相关的更有效的治疗方法的开发。

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