Molecules Great and Small: The Complement System

作者: Douglas R. Mathern , Peter S. Heeger

DOI: 10.2215/CJN.06230614

关键词: Complement receptorClassical complement pathwayAtypical hemolytic uremic syndromeImmunologyComplement component 5aMedicineAlternative complement pathwayAnaphylatoxinComplement component 3Complement system

摘要: The complement cascade, traditionally considered an effector arm of innate immunity required for host defense against pathogens, is now recognized as a crucial pathogenic mediator various kidney diseases. Complement components produced by the liver and circulating in plasma undergo activation through classical and/or mannose-binding lectin pathways to mediate anti-HLA antibody-initiated transplant rejection autoantibody-initiated GN, latter including membranous glomerulopathy, antiglomerular basement membrane disease, lupus nephritis. Inherited acquired abnormalities regulators, which requisitely limit restraint on alternative pathway activation, contribute pathogenesis C3 nephropathies atypical hemolytic uremic syndrome. Increasing evidence links endothelial cells tubular ischemia-reperfusion injury progressive fibrosis. Data emerging since mid-2000s additionally show that immune cells, T antigen-presenting produce during cognate interactions. subsequent local yields production anaphylatoxins C3a C5a, bind their respective receptors (C3aR C5aR) both partners augment T-cell proliferation survival, while simultaneously inhibiting regulatory induction function. This cell–derived enhances alloreactive results likely contributes other cell–mediated C5a/C5aR ligations neutrophils have been shown vascular inflammation models ANCA-mediated renal vasculitis. New translational immunology efforts along with development pharmacologic agents block human permit testing intriguing concept targeting patients assortment diseases has potential abrogate disease progression improve patient health.

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