A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis
A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis
复制标题
DOI：
10.1046/j.1365-2567.2002.01398.x
复制
发表时间：
2002-05-01
期刊：
影响因子：
6.4
通讯作者：
Nagaoka, I
中科院分区：
文献类型：
--
作者：
Niyonsaba, F;Iwabuchi, K;Nagaoka, I
肥大细胞是炎症反应中的主要效应细胞之一，可以在全身的大多数组织中发现。在炎症期间，局部环境中肥大细胞数量增加，并且这种积累需要该细胞群的定向迁移。由于先前已报道人凯萨林菌素衍生的抗菌肽LL-37刺激肥大细胞的脱粒，我们假设LL-37可能是肥大细胞趋化因子。目前的研究表明，LL-37是一种有效的肥大细胞趋化因子。趋化反应呈剂量依赖性和钟形，达到5 μ g/ml的最佳浓度。此外，棋盘格分析表明，细胞向这种肽的迁移是趋化性的，而不是趋化动力学。此外，使用（125）I标记的LL-37衍生肽的Scatchard分析显示，LL-37在肥大细胞上具有至少两类受体，即高亲和力和低亲和力受体。此外，竞争性结合试验表明，LL-37不太可能利用肥大细胞上的甲酰肽受体样1（FPRL 1），一种用于中性粒细胞和单核细胞迁移的功能性LL-37受体。此外，用百日咳毒素和磷脂酶C抑制剂U-73122处理细胞，抑制LL-37介导的迁移，表明LL-37通过Gi蛋白-磷脂酶C信号传导途径诱导肥大细胞趋化性。这些结果表明，除了抗菌活性外，LL-37还可能具有将肥大细胞募集到炎症灶的潜力。
The mast cell is one of the major effector cells in inflammatory reactions and can be found in most tissues throughout the body. During inflammation, an increase in the number of mast cells in the local milieu occurs, and such accumulation requires directed migration of this cell population. As it has previously been reported that the human cathelicidin-derived antibacterial peptide, LL-37, stimulates the degranulation of mast cells, we hypothesized that LL-37 could be a mast cell chemotaxin. The present study shows that LL-37 is a potent chemotactic factor for mast cells. The chemotactic response was dose-dependent and bell-shaped, reaching an optimal concentration of 5 mug/ml. In addition, checkerboard analysis showed that cell migration towards this peptide was chemotactic rather than chemokinetic. Moreover, Scatchard analysis using (125) I-labelled LL-37-derived peptide revealed that LL-37 has at least two classes of receptors, namely high- and low-affinity receptors, on mast cells. Furthermore, the competitive binding assay suggested that LL-37 is unlikely to utilize formyl peptide receptor-like 1 (FPRL1), a functional LL-37 receptor for neutrophil and monocyte migration, on mast cells. In addition, the treatment of cells with pertussis toxin and phospholipase C inhibitor, U-73122, inhibited LL-37-mediated migration, indicating that LL-37 induces mast cell chemotaxis through a Gi protein-phospholipase C signalling pathway. These results show that besides its antibacterial activities, LL-37 may have the potential to recruit mast cells to inflammation foci.