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.
Keywords:
MASP-1/3; complement; kidney.
© 2013 The Authors. Clinical and Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blotting, Western
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Complement Activation / immunology
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Complement C3 / immunology*
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Complement C3 / metabolism
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Complement C5 / immunology
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Complement C5 / metabolism
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Complement Factor B / immunology
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Complement Factor B / metabolism
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Complement Factor D / immunology
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Complement Factor D / metabolism
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Complement Factor H / deficiency*
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Complement Factor H / genetics
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Complement Factor H / immunology*
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Complement Pathway, Alternative / genetics
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Complement Pathway, Alternative / immunology
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Enzyme-Linked Immunosorbent Assay
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Glomerular Basement Membrane / immunology
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Glomerular Basement Membrane / metabolism
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Hereditary Complement Deficiency Diseases
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Kidney Diseases / blood
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Kidney Diseases / immunology*
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Kidney Glomerulus / immunology
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Kidney Glomerulus / metabolism
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Mannose-Binding Protein-Associated Serine Proteases / deficiency
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Mannose-Binding Protein-Associated Serine Proteases / genetics
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Mannose-Binding Protein-Associated Serine Proteases / immunology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
Substances
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Complement C3
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Complement C5
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Complement Factor H
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MASP-1 protein, mouse
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MASP-3 protein, mouse
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Mannose-Binding Protein-Associated Serine Proteases
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Complement Factor D
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Complement Factor B
Supplementary concepts
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Complement Factor H Deficiency