Leukocyte Cathepsin C Deficiency Attenuates Atherosclerotic Lesion Progression by Selective Tuning of Innate and Adaptive Immune Responses
| Autor: | Erik A.L. Biessen, Christine T.N. Pham, Mat J.A.P. Daemen, Sylvia Heeneman, Cora M.L. Beckers, Dianne J.M. Delsing, Mengyang Liao, Veronica Herias |
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| Přispěvatelé: | ACS - Amsterdam Cardiovascular Sciences, Pathology, Pathologie, Promovendi CD, RS: CARIM - R3 - Vascular biology, RS: SHE - R1 - Research (OvO) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Aortic arch
Carotid Artery Diseases Time Factors mice medicine.medical_treatment Aortic Diseases Down-Regulation Inflammation Biology Adaptive Immunity Lesion progression Cathepsin C Article Immune system medicine.artery medicine Leukocytes Animals Humans human Aorta Cells Cultured Mice Knockout Protease Cell Differentiation protease T helper cell T-Lymphocytes Helper-Inducer Macrophage Activation Immunity Innate Plaque Atherosclerotic Mice Inbred C57BL Haematopoiesis Disease Models Animal medicine.anatomical_structure Carotid Arteries Receptors LDL inflammation Immunology Cancer research Disease Progression Female medicine.symptom atherosclerosis Cardiology and Cardiovascular Medicine Foam Cells |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology, 35(1), 79-86. Lippincott Williams and Wilkins Arteriosclerosis Thrombosis and Vascular Biology, 35(1), 79-86. LIPPINCOTT WILLIAMS & WILKINS |
| ISSN: | 1524-4636 1079-5642 |
| Popis: | Objective— The protein degrading activity of cathepsin C (CatC), combined with its role in leukocyte granule activation, suggests a contribution of this cystein protease in atherosclerosis. However, no experimental data are available to validate this concept. Approach and Results— CatC gene and protein expression were increased in ruptured versus advanced stable human carotid artery lesions. To assess causal involvement of CatC in plaque progression and stability, we generated LDLr −/− //CatC −/− chimeras by bone marrow transplantation. CatC −/− chimeras presented attenuated plaque burden in carotids, descending aorta, aortic arch and root, at both the early and advanced plaque stage. CatC was abundantly expressed by plaque macrophages and foam cells. CatC expression and activity were dramatically downregulated in plaques of CatC −/− chimeras, supporting a hematopoietic origin of plaque CatC. Our studies unveiled an unexpected feedback of CatC deficiency on macrophage activation programs and T helper cell differentiation in as much as that CatC expression was upregulated in M1 macrophages, whereas its deficiency led to combined M2 (in vitro) and Th2 polarization (in vivo). Conclusions— Our data implicate CatC has a role in the selective tuning of innate and adaptive immune responses, relevant to a chronic immune disease, such as atherosclerosis. |
| Databáze: | OpenAIRE |
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