Le Yingying, Murphy Philip M, Wang Ji Ming
Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute at Frederick, MD 21702, USA.
Trends Immunol. 2002 Nov;23(11):541-8. doi: 10.1016/s1471-4906(02)02316-5.
Leukocytes accumulate at sites of inflammation and microbial infection in direct response to locally produced chemotactic factors, which signal through specific G protein-coupled receptors. The first chemotactic factors to be structurally defined were the N-formyl peptides. Unlike other leukocyte chemoattractants, N-formyl peptides could originate from either an endogenous source, such as the mitochondrial proteins of ruptured host cells, or an exogenous source, such as the proteins of invading pathogens. This suggests that the formyl-peptide receptor (FPR) and its variant FPRL1 (FPR-like 1) are involved in host defense against bacterial infection and in the clearance of damaged cells. Recently, additional, more complex, roles for these receptors have been proposed because FPR, and to a greater extent FPRL1, have been found to interact with a menagerie of structurally diverse pro- and anti-inflammatory ligands associated with different diseases, including amyloidosis, Alzheimer's disease, prion disease and HIV. How these receptors recognize such diverse ligands, which are the most important in vivo, and how they contribute to disease pathogenesis and host defense are basic questions currently under investigation that could lead to new therapeutic targets.
白细胞在局部产生的趋化因子的直接作用下，聚集在炎症和微生物感染部位，这些趋化因子通过特定的G蛋白偶联受体发出信号。最早在结构上被确定的趋化因子是N-甲酰肽。与其他白细胞趋化剂不同，N-甲酰肽可以来源于内源性物质，如破裂宿主细胞的线粒体蛋白，也可以来源于外源性物质，如入侵病原体的蛋白。这表明甲酰肽受体（FPR）及其变体FPRL1（FPR样1）参与宿主对细菌感染的防御以及受损细胞的清除。最近，有人提出这些受体还有其他更复杂的作用，因为已发现FPR，尤其是FPRL1，能与一系列结构多样的促炎和抗炎配体相互作用，这些配体与不同疾病相关，包括淀粉样变性、阿尔茨海默病、朊病毒病和艾滋病。这些受体如何识别体内最重要的如此多样的配体，以及它们如何导致疾病发病机制和宿主防御，是目前正在研究的基本问题，可能会带来新的治疗靶点。
