Yan Li1, Li Qin1, Qijun Bai1, Jingjing Zhang1, Ruixue Chen1, Kunpeng Song2. 1. Department of Cardiovascular Medicine Ward II, Zhengzhou Central Hospital Affiliated to Zhengzhou University, 16 North Tongbai Road, Zhongyuan District, Zhengzhou, 450000, Henan Province, China. 2. Department of Cardiovascular Medicine Ward II, Zhengzhou Central Hospital Affiliated to Zhengzhou University, 16 North Tongbai Road, Zhongyuan District, Zhengzhou, 450000, Henan Province, China. songkp@163.com.
Abstract
BACKGROUND: CD100 is an immune semaphorin family member that highly expressed on T cells, which take part in the development of acute myocardial infarction (AMI). Matrix metalloproteinases (MMPs) are important mediators for membrane-bound CD100 (mCD100) shedding from T cells to generate soluble CD100 (sCD100), which has immunoregulatory effect on T cells. The aim of this study was to investigate modulatory role of CD100 on CD8+ T cell activity in AMI patients. METHODS: Peripheral sCD100 and MMP-2 level, as well as mCD100 level on T cells was assessed in patients with stable angina pectoris (SAP), unstable angina pectoris (UAP), and AMI. The regulatory function of MMP-2 on mCD100 shedding, sCD100 formation, and cytotoxicity of CD8+ T cells was analyzed in direct and indirect contact co-culture system. RESULTS: AMI patients had higher peripheral sCD100 and lower mCD100 expression on CD8+ T cells in comparison with SAP, UAP, and controls. CD8+ T cells in AMI patients showed elevated direct cytotoxicity, enhanced cytokine production, and increased perforin/granzyme B secretion. Recombinant sCD100 stimulation promoted cytolytic function of CD8+ T cells in controls and AMI patients. Furthermore, AMI patients also had elevated circulating MMP-2 level. Recombinant MMP-2 stimulation induced mCD100 shedding from CD8+ T cells and sCD100 generation, resulting in enhancement of CD8+ T cell cytotoxicity in AMI patients. CONCLUSION: Up-regulation of MMP-2 might contribute to elevation of mCD100 shedding and sCD100 formation, leading to increased cytotoxicity CD8+ T cells in AMI patients.
BACKGROUND: CD100 is an immune semaphorin family member that highly expressed on T cells, which take part in the development of acute myocardial infarction (AMI). Matrix metalloproteinases (MMPs) are important mediators for membrane-bound CD100 (mCD100) shedding from T cells to generate soluble CD100 (sCD100), which has immunoregulatory effect on T cells. The aim of this study was to investigate modulatory role of CD100 on CD8+ T cell activity in AMI patients. METHODS: Peripheral sCD100 and MMP-2 level, as well as mCD100 level on T cells was assessed in patients with stable angina pectoris (SAP), unstable angina pectoris (UAP), and AMI. The regulatory function of MMP-2 on mCD100 shedding, sCD100 formation, and cytotoxicity of CD8+ T cells was analyzed in direct and indirect contact co-culture system. RESULTS: AMI patients had higher peripheral sCD100 and lower mCD100 expression on CD8+ T cells in comparison with SAP, UAP, and controls. CD8+ T cells in AMI patients showed elevated direct cytotoxicity, enhanced cytokine production, and increased perforin/granzyme B secretion. Recombinant sCD100 stimulation promoted cytolytic function of CD8+ T cells in controls and AMI patients. Furthermore, AMI patients also had elevated circulating MMP-2 level. Recombinant MMP-2 stimulation induced mCD100 shedding from CD8+ T cells and sCD100 generation, resulting in enhancement of CD8+ T cell cytotoxicity in AMI patients. CONCLUSION: Up-regulation of MMP-2 might contribute to elevation of mCD100 shedding and sCD100 formation, leading to increased cytotoxicity CD8+ T cells in AMI patients.
Entities:
Keywords:
Acute myocardial infarction; CD100; Immunoregulation; T lymphocytes
Authors: Bing Jie Li; Yu He; Ying Zhang; Yong Hong Guo; Yun Zhou; Pei Xin Zhang; Wei Wang; Jie Ru Zhao; Jin Ge Li; Wei Ze Zuo; Chao Fan; Zhan Sheng Jia Journal: J Int Med Res Date: 2017-01-12 Impact factor: 1.671
Authors: Carina Gröschel; André Sasse; Sebastian Monecke; Charlotte Röhrborn; Leslie Elsner; Michael Didié; Verena Reupke; Gertrude Bunt; Andrew H Lichtman; Karl Toischer; Wolfram-Hubertus Zimmermann; Gerd Hasenfuß; Ralf Dressel Journal: Front Immunol Date: 2018-11-15 Impact factor: 7.561