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Semin Respir Crit Care Med 2004; 25(5): 465-474
DOI: 10.1055/s-2004-836140
DOI: 10.1055/s-2004-836140
Pathogenesis of Pulmonary Vasculitis
Further Information
Publication History
Publication Date:
09 November 2004 (online)
Vasculitis is inflammation of blood vessels and can affect any type of vessel in any organ. Pulmonary vasculitis usually is a component of a systemic small vessel vasculitis. Three major forms of small vessel vasculitis that often affect the lungs are Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. These forms of vasculitis are strongly associated with antineutrophil cytoplasmic autoantibodies (ANCA) directed against enzymes contained in the primary granules of neutrophils and peroxidase-positive lysosomes of monocytes. This review discusses the evidence for a pathogenic role of ANCA. In vitro, ANCAs can activate cytokine-primed neutrophils and monocytes resulting in oxygen radical formation and release of lysosomal enzymes. In vivo, antimyeloperoxidase ANCA has been shown to induce crescentic glomerulonephritis and systemic vasculitis. Overall, the available data suggest that ANCA are indeed a pathogenic factor in the development of small-vessel vasculitis. Antiglomerular basement membrane (anti-GBM) disease also causes pulmonary vasculitis through immune attack on alveolar capillaries and glomerulonephritis through antibody mediated injury to glomerular capillaries. Thus, there is evidence that antibodies are important pathogenic factors in both ANCA disease and anti-GBM disease, however, there are also indications that T cells may play important pathogenic roles in both categories of disease as well.
KEYWORDS
Vasculitis - antineutrophil cytoplasmic autoantibodies - neutrophil - myeloperoxidase - proteinase 3
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J. Charles JennetteM.D.
Department of Pathology and Laboratory Medicine
Campus Box #7525, University of North Carolina at Chapel Hill
Chapel Hill, NC 27599-7525
Email: jcj@med.unc.edu