Vascular damage in giant cell arteritis

• Type of Material: Article
• Authors: Kisha Piggott, Emory University; Valerie Biousse, Emory University; Nancy Newman, Emory University; Jorg J. Goronzy, Emory University; Cornelia M. Weyand, Emory University
• Language: English
• Date: 2009-01-01
• Publisher: Taylor & Francis: STM, Behavioural Science and Public Health Titles
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © Informa UK Ltd.
• Final Published Version (URL): http://dx.doi.org/10.1080/08916930903002495
• Title of Journal or Parent Work: Autoimmunity
• ISSN: 0891-6934
• Volume: 42
• Issue: 7
• Start Page: 596
• End Page: 604
• Grant/Funding Information: This work was funded in part by grants from the National Institutes of Health (RO1 AR42527, RO1 AR41974, R01 AI44142, R01 AI57266, RO1 EY11916 and R01 AG15043), by core grant P30-EY06360 (Department of Ophthalmology) also from the National Institutes of Health, and by a departmental grant (Department of Ophthalmology) from Research to Prevent Blindness.
• Keywords: POLYMYALGIA-RHEUMATICA; macrophages; ANIMAL-MODEL; Immunology; CYTOKINES; Giant cell arteritis; Life Sciences & Biomedicine; VESSEL VASCULITIS; WALL; Science & Technology; T cell; ATHEROSCLEROSIS; Takayasu arteritis; DISEASE-ACTIVITY; TH17 CELLS; vascular smooth muscle cell; cytokines; endothelial cell; DENDRITIC CELLS; T-CELLS
• Research Categories: Health Sciences, Immunology; Biology, Cell

Abstract

Immune-mediated damage to medium-sized arteries results in wall remodeling with intimal hyperplasia, luminal stenosis and tissue ischemia. In the case of the aorta, vasculitis may result in dissection, aneurysm or rupture. The response-to-injury program of the blood vessel is a concerted action between the immune system and wall-resident cells, involving the release of growth and angiogenic factors from macrophages and giant cells and the migration and hyperproliferation of vascular smooth muscle cells. Innate immune cells, specifically, dendritic cells (DC) positioned in the vessel wall, have been implicated in the earliest steps of vasculitis. Pathogen-derived molecular patterns are capable of activating vascular DC and initiating adaptive immune responses. The pattern of the emerging vessel wall inflammation is ultimately determined by the initial insult. Ligands to toll-like receptor (TLR) 4, such as lipopolysaccharides, facilitate the recruitment of CD4 T cells that invade deep into the wall and distribute in a panarteritic pattern. Conversely, ligands for TLR5 condition vascular DC to support perivasculitic infiltrates. In essence, both innate and adaptive immune reactions collaborate to render the arterial wall susceptible to inflammatory damage. Unique features of the tissue microenvironment, including specialized DC, shape the course of the inflammatory response. Differences in vascular damage pattern encountered in different patients may relate to distinct instigators of vasculitis.