An annexin 1 N-terminal peptide activates leukocytes by triggering different members of the formyl peptide receptor family
An annexin 1 N-terminal peptide activates leukocytes by triggering different members of the formyl peptide receptor family
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DOI：
10.4049/jimmunol.172.12.7669
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发表时间：
2004-06-15
影响因子：
4.4
通讯作者：
Rescher, U
中科院分区：
文献类型：
--
作者：
Ernst, S;Lange, C;Rescher, U
人类N-甲酰肽受体(FPR)是趋化作用的关键调节剂，引导粒细胞向细菌感染部位移动。FPR是G蛋白偶联受体亚家族的创始成员，被认为在炎症过程中发挥作用。另外两个成员，FPRL(FPRL)1和FPRL2，对细菌肽的亲和力大大降低或根本不结合，FPRL2目前被认为是一个孤儿受体。在这项研究中，我们证明了来自抗炎蛋白Annexin 1(Lipocortin 1)N-末端结构域的多肽可以在相似浓度下激活所有三个FPR家族成员。膜联蛋白1肽在人类单核细胞中启动趋化反应，表达所有三个FPR家族成员，并使细胞对随后细菌多肽激动剂的刺激不敏感。用稳定表达单个FPR家族成员的HEK 293细胞进行的实验表明，这三种受体都可以被N端膜联蛋白1肽激活和脱敏。这些观察结果表明，膜联蛋白1肽是FPRL2的第一个内源性配体，并表明膜联蛋白1通过激活和脱敏FPRR家族的不同受体参与调节白细胞向炎症组织的迁移。
The human N-formyl peptide receptor (FPR) is a key modulator of chemotaxis directing granulocytes toward sites of bacterial infections. FPR is the founding member of a subfamily of G protein-coupled receptors thought to function in inflammatory processes. The other two members, FPR-like (FPRL)1 and FPRL2, have a greatly reduced affinity for bacterial peptides or do not bind them at all, with FPRL2 being considered an orphan receptor so far. In this study we show that a peptide derived from the N-terminal domain of the anti-inflammatory protein annexin 1 (lipocortin 1) can activate all three FPR family members at similar concentrations. The annexin 1 peptide initiates chemotactic responses in human monocytes that express all three FPR family members and also desensitizes the cells toward subsequent stimulation with bacterial peptide agonists. Experiments using HEK 293 cells stably expressing a single FPR family member reveal that all three receptors can be activated and desensitized by the N-terminal annexin 1 peptide. These observations identify the annexin 1 peptide as the first endogenous ligand of FPRL2 and indicate that annexin 1 participates in regulating leukocyte emigration into inflamed tissue by activating and desensitizing different receptors of the FPR family.