FAM19A4 is a novel cytokine ligand of formyl peptide receptor 1 (FPR1) and is able to promote the migration and phagocytosis of macrophages
FAM19A4 is a novel cytokine ligand of formyl peptide receptor 1 (FPR1) and is able to promote the migration and phagocytosis of macrophages
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DOI：
10.1038/cmi.2014.61
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发表时间：
2015-09-01
影响因子：
24.1
通讯作者：
Han, Wenling
中科院分区：
文献类型：
--
作者：
Wang, Wenyan;Li, Ting;Han, Wenling
FAM 19 A4是具有序列相似性的家族19（趋化因子（C-C基序）样）成员A4的缩写，其是在正常组织中以低水平表达的分泌蛋白。FAM 19 A4的生物学功能仍有待确定，其潜在的受体尚不清楚。本研究证明FAM 19 A4是一种经典的分泌蛋白，并首次证实其成熟蛋白由95个氨基酸组成。我们发现，这种新的细胞因子的表达上调脂多糖（LPS）刺激的单核细胞和巨噬细胞，通常是在极化M1。FAM 19 A4在体外和体内均表现出对巨噬细胞的趋化活性，并增强巨噬细胞对酵母聚糖的吞噬作用，同时显著增加蛋白激酶B（Akt）的磷酸化。FAM 19 A4还可以增加酵母聚糖刺激后活性氧（ROS）的释放。此外，基于受体内化、放射性配体结合试验和受体阻断，我们首次证明FAM 19 A4是甲酰基肽受体1（FPR 1）的新配体。上述数据表明，在炎症刺激时，单核细胞/巨噬细胞衍生的FAM 19 A4可能在病原性感染期间巨噬细胞的迁移和活化中起关键作用。
FAM19A4 is an abbreviation for family with sequence similarity 19 (chemokine (C-C motif)-like) member A4, which is a secretory protein expressed in low levels in normal tissues. The biological functions of FAM19A4 remain to be determined, and its potential receptor(s) is unclarified. In this study, we demonstrated that FAM19A4 was a classical secretory protein and we verified for the first time that its mature protein is composed of 95 amino acids. We found that the expression of this novel cytokine was upregulated in lipopolysaccharide (LPS)-stimulated monocytes and macrophages and was typically in polarized M1. FAM19A4 shows chemotactic activities on macrophages and enhances the macrophage phagocytosis of zymosan both in vitro and in vivo with noticeable increases of the phosphorylation of protein kinase B (Akt). FAM19A4 can also increase the release of reactive oxygen species (ROS) upon zymosan stimulation. Furthermore, based on receptor internalization, radio ligand binding assays and receptor blockage, we demonstrated for the first time that FAM19A4 is a novel ligand of formyl peptide receptor 1 (FPR1). The above data indicate that upon inflammatory stimulation, monocyte/macrophage-derived FAM19A4 may play a crucial role in the migration and activation of macrophages during pathogenic infections.