Modulation of neutrophil apoptosis by antimicrobial peptides.
Modulation of neutrophil apoptosis by antimicrobial peptides.
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DOI：
10.5402/2012/345791
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Hirata M
中科院分区：
文献类型：
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作者：
Nagaoka I;Suzuki K;Niyonsaba F;Tamura H;Hirata M
肽类抗生素具有很强的抗微生物活性，有助于宿主的天然防御。人抗菌肽、α-防御素（人中性粒细胞肽，HNP）、人β-防御素（hBD）和凯萨林菌素（LL-37）不仅对革兰氏阴性和革兰氏阳性细菌表现出有效的杀菌活性，而且通过诱导细胞因子和趋化因子的产生以及炎症和免疫细胞活化而作为免疫调节分子发挥作用。中性粒细胞是宿主防御微生物感染的关键效应细胞，其寿命受各种病原体和宿主衍生物质的调节。在这里，我们提供了证据表明，HNP-1，hBD-3和LL-37不仅可以破坏细菌，而且还可以有效地调节（抑制）中性粒细胞凋亡，伴随ERK-1/-2磷酸化，tBid下调（一种促凋亡蛋白）和Bcl-xL的上调（一种抗凋亡蛋白），以及抑制线粒体膜电位变化和半胱天冬酶3活性，可能通过对不同受体的作用，P2 Y 6核苷酸受体、趋化因子受体CCR 6和低亲和力甲酰肽受体FPRL 1/核苷酸受体P2 X7。抑制中性粒细胞凋亡导致其寿命延长，可能有利于宿主防御细菌入侵。
Peptide antibiotics possess the potent antimicrobial activities against invading microorganisms and contribute to the innate host defense. Human antimicrobial peptides, α-defensins (human neutrophil peptides, HNPs), human β-defensins (hBDs), and cathelicidin (LL-37) not only exhibit potent bactericidal activities against Gram-negative and Gram-positive bacteria, but also function as immunomodulatory molecules by inducing cytokine and chemokine production, and inflammatory and immune cell activation. Neutrophil is a critical effector cell in host defense against microbial infection, and its lifespan is regulated by various pathogen- and host-derived substances. Here, we provided the evidence that HNP-1, hBD-3, and LL-37 cannot only destroy bacteria but also potently modulate (suppress) neutrophil apoptosis, accompanied with the phosphorylation of ERK-1/-2, the downregulation of tBid (an proapoptotic protein) and upregulation of Bcl-xL (an antiapoptotic protein), and the inhibition of mitochondrial membrane potential change and caspase 3 activity, possibly via the actions on the distinct receptors, the P2Y6 nucleotide receptor, the chemokine receptor CCR6, and the low-affinity formyl-peptide receptor FPRL1/the nucleotide receptor P2X7, respectively. Suppression of neutrophil apoptosis results in the prolongation of their lifespan and may be advantageous for the host defense against bacterial invasion.