Monocyte Chemoattractant Protein-1 (MCP-1) Regulates Macrophage Cytotoxicity in Abdominal Aortic Aneurysm
| العنوان: | Monocyte Chemoattractant Protein-1 (MCP-1) Regulates Macrophage Cytotoxicity in Abdominal Aortic Aneurysm |
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| المؤلفون: | Jun Ren, Bo Liu, Zhenjie Liu, Changlin Dou, Qiwei Wang, Stephanie Morgan |
| المصدر: | PLoS ONE, Vol 9, Iss 3, p e92053 (2014) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Male, Pathology, Physiology, lcsh:Medicine, Apoptosis, 030204 cardiovascular system & hematology, Vascular Medicine, Fas ligand, Mice, 0302 clinical medicine, Cell Signaling, Immune Physiology, Molecular Cell Biology, Medicine and Health Sciences, Cytotoxic T cell, Macrophage, lcsh:Science, Immune Response, Chemokine CCL2, Apoptotic Signaling Cascade, Apoptotic Signaling, Caspase 8, 0303 health sciences, Multidisciplinary, Cell Death, Caspase 3, CD68, GTPase-Activating Proteins, musculoskeletal system, Signaling Cascades, Cell Processes, cardiovascular system, Cytokines, Anatomy, Research Article, Signal Transduction, medicine.medical_specialty, Programmed cell death, Fas Ligand Protein, Myocytes, Smooth Muscle, Immunology, Cardiology, Biology, Cell Line, 03 medical and health sciences, medicine, Animals, Vascular Diseases, 030304 developmental biology, Inflammation, Macrophages, lcsh:R, Biology and Life Sciences, Cell Biology, Molecular Development, Molecular biology, Coculture Techniques, Gene Expression Regulation, Peripheral Vascular Disease, Immune System, Cardiovascular Anatomy, lcsh:Q, Aortic Aneurysm, Abdominal, Developmental Biology |
| الوصف: | Aims In abdominal aortic aneurysm (AAA), macrophages are detected in the proximity of aortic smooth muscle cells (SMCs). We have previously demonstrated in a murine model of AAA that apoptotic SMCs attract monocytes and other leukocytes by producing MCP-1. Here we tested whether infiltrating macrophages also directly contribute to SMC apoptosis. Methods and Results Using a SMC/RAW264.7 macrophage co-culture system, we demonstrated that MCP-1-primed RAWs caused a significantly higher level of apoptosis in SMCs as compared to control macrophages. Next, we detected an enhanced Fas ligand (FasL) mRNA level and membrane FasL protein expression in MCP-1-primed RAWs. Neutralizing FasL blocked SMC apoptosis in the co-culture. In situ proximity ligation assay showed that SMCs exposed to primed macrophages contained higher levels of receptor interacting protein-1 (RIP1)/Caspase 8 containing cell death complexes. Silencing RIP1 conferred apoptosis resistance to SMCs. In the mouse elastase injury model of aneurysm, aneurysm induction increased the level of RIP1/Caspase 8 containing complexes in medial SMCs. Moreover, TUNEL-positive SMCs in aneurysmal tissues were frequently surrounded by CD68+/FasL+ macrophages. Conversely, elastase-treated arteries from MCP-1 knockout mice display a reduction of both macrophage infiltration and FasL expression, which was accompanied by diminished apoptosis of SMCs. Conclusion Our data suggest that MCP-1-primed macrophages are more cytotoxic. MCP-1 appears to modulate macrophage cytotoxicity by increasing the level of membrane bound FasL. Thus, we showed that MCP-1-primed macrophages kill SMCs through a FasL/Fas-Caspase8-RIP1 mediated mechanism. |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3faf09290ac102ff70203d82a23a269c https://doi.org/10.1371/journal.pone.0092053 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....3faf09290ac102ff70203d82a23a269c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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