Pleurocidin, a novel antimicrobial peptide, induces human mast cell activation through the FPRL1 receptor
Pleurocidin, a novel antimicrobial peptide, induces human mast cell activation through the FPRL1 receptor
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DOI：
10.1038/mi.2013.37
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发表时间：
2014-01-01
影响因子：
8
通讯作者：
Kulka, M.
中科院分区：
文献类型：
--
作者：
Pundir, P.;Catalli, A.;Kulka, M.
杀菌素是一类新型的α-螺旋阳离子抗菌肽(CAP)家族，其结构和功能与主要的CAP家族之一的杀菌素相似。由于放线菌素刺激肥大细胞的趋化和介质的释放，我们推测，杀胸菌素类似地激活肥大细胞。对20个杀胸腺素肽的筛选表明，其中一些能够使人肥大细胞系LAD2(过敏性疾病实验室2)脱颗粒。杀菌素NRC-04导致LAD2黏附、迁移、脱颗粒和释放半胱氨酰白三烯和前列腺素D-2。此外，杀胸菌素还可促进肥大细胞内钙离子的动员，并诱导单核细胞趋化蛋白-1/C-C基序趋化因子配体2(CCL2)和巨噬细胞炎性蛋白-1β/CCL4等促炎趋化因子的产生。我们对可能的细胞机制的评估表明，G蛋白、磷脂酶C和磷脂酶C参与了胸膜毒素诱导的肥大细胞活化，百日咳毒素(G蛋白抑制剂)、Wortmanin(PI3K抑制剂)、U-73122(磷脂酶C抑制剂)和Ro-31-8220(蛋白激酶C抑制剂)分别抑制了G蛋白、磷脂酶C和磷脂酶C的激活。我们还发现，人肥大细胞表达N-甲酰基多肽受体1(FPRL1)受体，FPRL1特异性抑制物影响胸苷肽介导的肥大细胞活化。我们的发现表明，新的CAP胸腔杀菌素通过G蛋白偶联受体信号通路激活人肥大细胞，提示该多肽可能具有免疫调节功能。
Pleurocidins are a novel family of alpha-helical cationic antimicrobial peptides (CAPs) that are structurally and functionally similar to cathelicidins, one of the major CAP families. As cathelicidins stimulate mast cell chemotaxis and mediator release, we postulated that pleurocidins similarly activate mast cells. A screen of 20 pleurocidin peptides revealed that some were capable of degranulating the human mast cell line LAD2 (Laboratory of Allergic Diseases 2). Pleurocidin NRC- 04 caused LAD2 to adhere, migrate, degranulate, and release cysteinyl leukotrienes and prostaglandin D-2. Moreover, pleurocidin increased intracellular Ca2+ mobilization in mast cells and induced the production of proinflammatory chemokines such as monocyte chemotactic protein-1/C-C motif chemokine ligand 2 (CCL2) and macrophage inflammatory protein-1 beta/CCL4. Our evaluation of possible cellular mechanisms suggested that G proteins, phosphoinositol-3 kinase (PI3K), phospholipase C (PLC), and phosphokinase C (PKC) were involved in pleurocidininduced mast cell activation as evidenced by the inhibitory effects of pertussis toxin (G protein inhibitor), wortmanin (PI3K inhibitor), U-73122 (PLC inhibitor), and Ro-31-8220 (PKC inhibitor), respectively. We also found that human mast cells expressed the N-formyl-peptide receptor 1 (FPRL1) receptor and FPRL1-specific inhibitor affected pleurocidin-mediated activation of mast cell. Our finding that the novel CAP pleurocidin activated human mast cell through G protein-coupled receptor signaling suggests that this peptide might have immunomodulatory functions.