期刊
AUTOIMMUNITY REVIEWS
卷 3, 期 1, 页码 46-53出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/S1568-9972(03)00064-8
关键词
T cells; dendritic cells; macrophages; intimal hyperplasia; acute phase response
类别
资金
- NEI NIH HHS [R01 EY11916] Funding Source: Medline
- NHLBI NIH HHS [R01 HL 63919] Funding Source: Medline
- NIAID NIH HHS [R01 AI44142] Funding Source: Medline
- NIAMS NIH HHS [R01 AR42527, R01 AR41974] Funding Source: Medline
- NIA NIH HHS [R01 AG15043] Funding Source: Medline
- NATIONAL EYE INSTITUTE [R01EY011916] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL063919] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI044142] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR042527, R01AR041974] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R01AG015043] Funding Source: NIH RePORTER
Giant cell arteritis (GCA), a vasculitis that targets medium- and large-size arteries, is ranked as a medical emergency because of its potential to cause blindness and stroke. The typical lesions, granulomas in the vessel wall, are formed by IFN-gamma-producing CD4(+) T cells and macrophages. CD4(+) T cells undergo in situ activation in the adventitia, where they interact with indigenous dendritic cells. Tissue injury is mediated by several distinct sets of macrophages that are committed to diverse effector functions. The dominant tissue injury in the media results from oxidative stress and leads to smooth muscle cell apoptosis and nitration of endothelial cells. Macrophage-derived growth factors are instrumental in driving the response-to-injury program of the artery that causes intimal hyperplasia and vessel occlusion. Clinical manifestations are those of tissue ischemia or a syndrome of exuberant systemic inflammation. The vascular and the systemic components of GCA contribute differentially to the disease, leading to distinct clinical phenotypes of this arteritis. Immunologically most interesting is polymyalgia rheumatica, in which the systemic component is combined with aborted vasculitis, suggesting a role for artery-specific tolerance mechanisms. (C) 2003 Elsevier Science B.V. All rights reserved.
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