Chen Q, Schmidt A P, Anderson G M, Wang J M, Wooters J, Oppenheim J J, Chertov O
Laboratory of Molecular Immunoregulation, Division of Basic Sciences, Frederick, MD, USA.
J Exp Med. 2000 Oct 2;192(7):1069-74. doi: 10.1084/jem.192.7.1069.
We have previously shown that antimicrobial peptides like defensins have the capacity to mobilize leukocytes in host defense. LL-37 is the cleaved antimicrobial 37-residue, COOH-terminal peptide of hCAP18 (human cationic antimicrobial protein with a molecular size of 18 kD), the only identified member in humans of a family of proteins called cathelicidins. LL-37/hCAP18 is produced by neutrophils and various epithelial cells. Here we report that LL-37 is chemotactic for, and can induce Ca(2+) mobilization in, human monocytes and formyl peptide receptor-like 1 (FPRL1)-transfected human embryonic kidney 293 cells. LL-37-induced Ca(2+) mobilization in monocytes can also be cross-desensitized by an FPRL1-specific agonist. Furthermore, LL-37 is also chemotactic for human neutrophils and T lymphocytes that are known to express FPRL1. Our results suggest that, in addition to its microbicidal activity, LL-37 may contribute to innate and adaptive immunity by recruiting neutrophils, monocytes, and T cells to sites of microbial invasion by interacting with FPRL1.
我们之前已经表明，防御素等抗菌肽在宿主防御中具有调动白细胞的能力。LL-37是hCAP18（分子大小为18 kD的人阳离子抗菌蛋白）经切割产生的含37个残基的抗菌性C末端肽，hCAP18是人类中唯一已鉴定的一类称为cathelicidins的蛋白质家族成员。LL-37/hCAP18由中性粒细胞和各种上皮细胞产生。在此我们报告，LL-37对人单核细胞以及转染了甲酰肽受体样1（FPRL1）的人胚肾293细胞具有趋化作用，并能诱导其Ca(2+)动员。LL-37诱导的单核细胞Ca(2+)动员也可被FPRL1特异性激动剂交叉脱敏。此外，LL-37对已知表达FPRL1的人中性粒细胞和T淋巴细胞也具有趋化作用。我们的结果表明，除了其杀菌活性外，LL-37可能通过与FPRL1相互作用，将中性粒细胞、单核细胞和T细胞招募到微生物入侵部位，从而对先天免疫和适应性免疫做出贡献。
