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FAM19A4 is a novel cytokine ligand of formyl peptide receptor I （fpr 1） and is able to promote the migration and phagocytosis of macrophages

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Cellular & Molecular Immunology 2015年第5期12卷 615-624页

作者： Wenyan Wang Ting Li Xiaolin Wang Wanxiong Yuan Yingying Cheng Heyu Zhang Enquan Xu Yingmei Zhang Shuang Shi Dalong Ma Wenling Han Department of Immunology School of Basic Medical Sciences Peking University Health Science Center Peking University Center for Human Disease Genomics Key Laboratory of Medical Immunology Ministry of Health Beijing China Department of Microbiologyand Infectious Disease Center School of Basic Medical Sciences Peking University Health Science Center Beijing China

FAM 19A4 is an abbreviation for family with sequence similarity 19 （chemokine （C-C motif）-Iike） 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 FAM 19A4 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 M 1. FAM 19A4 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）. FAM 19A4 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 FAM 19A4 may play a crucial role in the migration and activation of macrophages during pathogenic infections.

关键词： cytokine FAM 19A4 fpr 1 macrophages phagocytosis

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