The importance of resolution of inflammation in the pathogenesis of ANCA-associated vasculitis.
The primary small-vessel systemic vasculitides are disorders that target small blood vessels, inducing vessel wall inflammation, and are associated with the development of anti-neutrophil cytoplasmic antibodies. Multiple organs are attacked, including the lungs and kidneys. Increasing knowledge of pathogenesis suggests that the antibodies activate neutrophils inappropriately, leading to endothelial and vascular damage. Cytokines, such as tumour necrosis factor, can facilitate damage by priming the neutrophils and activating endothelial cells. Apoptosis of infiltrating neutrophils is also disrupted by anti-neutrophil cytoplasmic antibody activation, and removal of these effete cells occurs in a pro-inflammatory manner, promoting persistent inflammation. The autoimmune response may be promoted by aberrant phagocytosis of apoptotic neutrophils by dendritic cells. Understanding the pathogenesis can help to rationalize existing therapies and indicate new approaches to therapy.
Harper
L
L
Division of Medical Sciences, University of Birmingham, Birmingham B15 2TT, UK. l.harper@bham.ac.uk
Williams
J M
JM
Savage
C O
CO
D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000737:chemistry* / Q000378:metabolism; D017951:Antigen Presentation; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000382:microbiology; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D009504:Neutrophils / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha; D014657:Vasculitis / Q000473:pathology*
D019268:Antibodies, Antineutrophil Cytoplasmic; D014409:Tumor Necrosis Factor-alpha; D019869:Phosphatidylinositol 3-Kinases