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Angiotensin II–C–C chemokine receptor2/5 axis‐dependent monocyte/macrophage recruitment contributes to progression of experimental autoimmune myocarditis
Author(s) -
Lu Hongxiang,
Zong Gangjun,
Zhou Shanshan,
Jiang Yuanyuan,
Chen Rong,
Su Zhaoliang,
Wu Yan
Publication year - 2017
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/1348-0421.12548
Subject(s) - ccr2 , chemokine , monocyte , angiotensin ii , macrophage , immunology , biology , cc chemokine receptors , ccl2 , inflammation , chemokine receptor , receptor , biochemistry , in vitro
Angiotensin II (ANG II) plays critical roles in modulation of circulatory homeostasis and activation of innate and adaptive immunity and has also been implicated in several mouse models of autoimmune disease. However, how ANG II regulates macrophages and is involved in development of experimental autoimmune myocarditis (EAM) remains unclear. Therefore, the present study aimed to address the above question and explore possible mechanisms. EAM was induced in BALB/c mice. ANG II was quantitated by ELISA and hematoxylin and eosin staining was employed to analyze pathological changes and macrophage infiltration. The chemotactic ability of ANG II was assessed by using a Transwell system. It was found that ANG II is up‐regulated in serum and heart tissues of mice with EAM and that ANG II significantly drives monocyte/macrophage infiltration through the C‐C chemokine receptor 2/5 (CCR2/5) axis. CCR2/5 antagonists and ANG II receptor inhibitor could all abrogate monocyte/macrophage infiltration and ameliorate development of EAM. Our results have firstly identified a novel function of ANG II: that it is a critical chemokine for monocyte/macrophage recruitment. Furthermore, our results indicate that ANG II is a potential candidate for treatment of inflammatory diseases.