Human adenosine deaminase 2 induces differentiation of monocytes into macrophages and stimulates proliferation of T helper cells and macrophages

Journal of Leukocyte Biology

Andrey V. Zavialov⁴  Grégoire Lauvau²  Nicolas Glaichenhaus²  Anton V. Zavialov³  Eduard Gracia¹  Rafael Franco¹ 

[1] Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), and Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), and Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), and Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain;Institut National de la Santé et de la Recherche Médicale U924, University of Nice-Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France; Institut National de la Santé et de la Recherche Médicale U924, University of Nice-Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France; Institut National de la Santé et de la Recherche Médicale U924, University of Nice-Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France;;Department of Molecular Biology, Uppsala Biomedical Centre, Swedish University of Agricultural Sciences, Uppsala, Sweden; and Department of Molecular Biology, Uppsala Biomedical Centre, Swedish University of Agricultural Sciences, Uppsala, Sweden; and Department of Molecular Biology, Uppsala Biomedical Centre, Swedish University of Agricultural Sciences, Uppsala, Sweden; and;Institut National de la Santé et de la Recherche Médicale U924, University of Nice-Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France; Laboratory of Immune Regulation, Singapore Immunology Network (SlgN), Singapore Institut National de la Santé et de la Recherche Médicale U924, University of Nice-Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France; Institut National de la Santé et de la Recherche Médicale U924, University of Nice-Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France; Laboratory of Immune Regulation, Singapore Immunology Network (SlgN), Singapore Laboratory of Immune Regulation, Singapore Immunology Network (SlgN), Singapore Institut National de la Santé et de la Recherche Médicale U924, University of Nice-Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France; Laboratory of Immune Regulation, Singapore Immunology Network (SlgN), Singapore

关键词: innate immunity;    adaptive immunity;    development;   

DOI  :  10.1189/jlb.1109764

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ADAs play a pivotal role in regulating the level of adenosine, a signaling molecule controlling a variety of cellular responses by binding to and activating four ADRs. Two enzymes, ADA1 and ADA2, are known to possess ADA activity in humans. Although the structure of ADA1 and its role in lymphocytic activation have been known for a long time, the structure and function of ADA2, a member of ADGF, remain enigmatic. Here, we found that ADA2 is secreted by monocytes undergoing differentiation into macrophages or DCs and that it binds to the cell surface via proteoglycans and ADRs. We demonstrate that ADA1 and ADA2 increase the rate of proliferation of monocyte-activated CD4+ T cells independently of their catalytic activity. We also show that ADA2 induces T cell-dependent differentiation of monocytes into macrophages and stimulates macrophage proliferation. Our discovery of the growth factor-like activity of ADA2 explains clinical observations and suggests that this enzyme could be used as a drug candidate to modulate the immune responses during inflammation and cancer.

【 授权许可】

Unknown