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FAM19A4 is a novel cytokine ligand of formyl peptide receptor 1 (FPR1) and is able to promote the migration and phagocytosis of macrophages

Cellular & Molecular Immunology volume 12, pages 615–624 (2015)Cite this article

Abstract

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.

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Acknowledgements

We thank Professor Philip M Murphy from the Laboratory of Molecular Immunology, National Institutes of Health for providing the plasmid pCMV-FPR1. We also thank Li Yan, PhD, of the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London for his contributions to the statistical analyses in this work. This work was supported by grants from the National Natural Science Foundation of China (81273233) and the Peking University–National Taiwan University Cooperation Fund (BMU20120316).

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Author notes

  1. Professor WL Han, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China. E-mail: hanwl@bjmu.edu.cn

Authors and Affiliations

  1. 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,

    Wenyan Wang, Ting Li, Xiaolin Wang, Wanxiong Yuan, Yingying Cheng, Heyu Zhang, Enquan Xu, Yingmei Zhang, Dalong Ma & Wenling Han

  2. Peking University Center for Human Disease Genomics, Key Laboratory of Medical Immunology, Ministry of Health, Beijing, China

    Wenyan Wang, Ting Li, Xiaolin Wang, Wanxiong Yuan, Yingying Cheng, Heyu Zhang, Enquan Xu, Yingmei Zhang, Dalong Ma & Wenling Han

  3. Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China

    Shuang Shi

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Wang, W., Li, T., Wang, X. et al. FAM19A4 is a novel cytokine ligand of formyl peptide receptor 1 (FPR1) and is able to promote the migration and phagocytosis of macrophages. Cell Mol Immunol 12, 615–624 (2015). https://doi.org/10.1038/cmi.2014.61

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