Reciprocal Interaction between Macrophages and T cells Stimulates IFN-γ and MCP-1 Production in Ang II-induced Cardiac Inflammation and Fibrosis

PLoS One

Yong-fen Qi¹  Li-xin Jia¹  Ji-zhong Cheng¹  Jie Du¹  Ya-lei Han¹  Yu-lin Li¹  Hong-jia Zhang² 

[1] Beijing An Zhen Hospital, Capital Medical University, Beijing, China;The Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education, Institute of Heart Lung and Blood Vessel Diseases, Beijing, China

关键词: Macrophages;    T cells;    Heart;    Inflammation;    Fibrosis;    Cytokines;    Flow cytometry;    Inflammatory diseases;   

DOI  :  10.1371/journal.pone.0035506

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Background The inflammatory response plays a critical role in hypertension-induced cardiac remodeling. We aimed to study how interaction among inflammatory cells causes inflammatory responses in the process of hypertensive cardiac fibrosis. Methodology/Principal Findings Infusion of angiotensin II (Ang II, 1500 ng/kg/min) in mice rapidly induced the expression of interferon γ (IFN-γ) and leukocytes infiltration into the heart. To determine the role of IFN-γ on cardiac inflammation and remodeling, both wild-type (WT) and IFN-γ-knockout (KO) mice were infused Ang II for 7 days, and were found an equal blood pressure increase. However, knockout of IFN-γ prevented Ang II-induced: 1) infiltration of macrophages and T cells into cardiac tissue; 2) expression of tumor necrosis factor α and monocyte chemoattractant protein 1 (MCP-1), and 3) cardiac fibrosis, including the expression of α-smooth muscle actin and collagen I (all p<0.05). Cultured T cells or macrophages alone expressed very low level of IFN-γ, however, co-culture of T cells and macrophages increased IFN-γ expression by 19.8±0.95 folds (vs. WT macrophage, p<0.001) and 20.9 ± 2.09 folds (vs. WT T cells, p<0.001). In vitro co-culture studies using T cells and macrophages from WT or IFN-γ KO mice demonstrated that T cells were primary source for IFN-γ production. Co-culture of WT macrophages with WT T cells, but not with IFN-γ-knockout T cells, increased IFN-γ production (p<0.01). Moreover, IFN-γ produced by T cells amplified MCP-1 expression in macrophages and stimulated macrophage migration. Conclusions/Significance Reciprocal interaction between macrophages and T cells in heart stimulates IFN-γ expression, leading to increased MCP-1 expression in macrophages, which results a forward-feed recruitment of macrophages, thus contributing to Ang II-induced cardiac inflammation and fibrosis.

【 授权许可】

CC BY