title: C3 dysregulation due to factor H deficiency is mannan-binding lectin-associated serine proteases (MASP)-1 and MASP-3 independent in vivo.
abstract: Uncontrolled activation of the complement alternative pathway is associated with complement-mediated renal disease. Factor B and factor D are essential components of this pathway, while factor H (FH) is its major regulator. In complete FH deficiency, uncontrolled C3 activation through the alternative pathway results in plasma C3 depletion and complement-mediated renal disease. These are dependent on factor B. Mannan-binding lectin-associated serine proteases 1 and 3 (MASP-1, MASP-3) have been shown recently to contribute to alternative pathway activation by cleaving pro-factor D to its active form, factor D. We studied the contribution of MASP-1 and MASP-3 to uncontrolled alternative pathway activation in experimental complete FH deficiency. Co-deficiency of FH and MASP-1/MASP-3 did not ameliorate either the plasma C3 activation or glomerular C3 accumulation in FH-deficient mice. Our data indicate that MASP-1 and MASP-3 are not essential for alternative pathway activation in complete FH deficiency.
authors.affiliation: Centre for Complement & Inflammation Research, Imperial College London, London, UK.
authors.forename: M M
authors.initials: MM
authors.lastname: Ruseva
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Fujita
authors.forename: M C
authors.initials: MC
authors.lastname: Pickering
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003167:Complement Activation / Q000276:immunology; D003176:Complement C3 / Q000276:immunology* / Q000378:metabolism; D003182:Complement C5 / Q000276:immunology / Q000378:metabolism; D011415:Complement Factor B / Q000276:immunology / Q000378:metabolism; D011416:Complement Factor D / Q000276:immunology / Q000378:metabolism; D017242:Complement Factor H / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*; D003170:Complement Pathway, Alternative / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D050533:Glomerular Basement Membrane / Q000276:immunology / Q000378:metabolism; D000081208:Hereditary Complement Deficiency Diseases; D007674:Kidney Diseases / Q000097:blood / Q000276:immunology*; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015432:Glomerulonephritis, Membranoproliferative
chemical_list: D003176:Complement C3; D003182:Complement C5; D017242:Complement Factor H; C577328:MASP-1 protein, mouse; C468572:MASP-3 protein, mouse; D050606:Mannose-Binding Protein-Associated Serine Proteases; D011416:Complement Factor D; D011415:Complement Factor B
keywords: MASP-1/3; complement; kidney