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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2010-10-21
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pubmed:abstractText |
Gene-targeted mice deficient in the complement mannose-binding lectin-associated serine protease-1 and -3 (MASP1/3(-/-)) express only the zymogen of factor D (pro-factor D [pro-Df]), a necessary component of the alternative pathway (AP). We used the murine collagen Ab-induced arthritis (CAIA) model, in which the AP is unique among complement pathways in being both necessary and sufficient for disease induction, to determine whether MASP-1/3 are required in vivo for the development of tissue injury. Disease activity scores, complement C3 tissue deposition in the joint, and histopathologic injury scores were markedly decreased in MASP1/3(-/-) as compared with wild-type (WT) mice. MASP-1 protein was immunochemically localized to synovial cells of knees of WT mice with arthritis. Pro-Df was present in both synovial cells and chondrocytes of knees of WT and MASP1/3(-/-) mice without arthritis, with increased amounts present in synovial cells of WT mice with CAIA. No conversion of pro-Df to mature Df was detectable in the serum of MASP1/3(-/-) mice during the evolution of CAIA. C3 activation and deposition as well as C5a generation induced in vitro by adherent anti-type II collagen mAbs were absent using sera from MASP1/3(-/-) mice under conditions in which only the AP was active. The addition of human Df fully reconstituted in vitro C3 activation and C5a generation using sera from MASP1/3(-/-) mice. Our studies demonstrate for the first time, to our knowledge, the absolute requirement for the activity of MASP-1 protein in autoimmune-associated inflammatory tissue injury in vivo through activation of the AP of complement by cleavage of pro-Df to mature Df.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20870940-10092804,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20870940-10330290,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20870940-10605604,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20870940-9087411
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1550-6606
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
185
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5598-606
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pubmed:dateRevised |
2011-8-25
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pubmed:meshHeading |
pubmed-meshheading:20870940-Animals,
pubmed-meshheading:20870940-Arthritis, Experimental,
pubmed-meshheading:20870940-Blotting, Western,
pubmed-meshheading:20870940-Complement Factor D,
pubmed-meshheading:20870940-Complement Pathway, Alternative,
pubmed-meshheading:20870940-Female,
pubmed-meshheading:20870940-Humans,
pubmed-meshheading:20870940-Immunohistochemistry,
pubmed-meshheading:20870940-Male,
pubmed-meshheading:20870940-Mannose-Binding Protein-Associated Serine Proteases,
pubmed-meshheading:20870940-Mice,
pubmed-meshheading:20870940-Mice, Inbred C57BL,
pubmed-meshheading:20870940-Mice, Knockout,
pubmed-meshheading:20870940-Polymerase Chain Reaction
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pubmed:year |
2010
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pubmed:articleTitle |
Essential role of complement mannose-binding lectin-associated serine proteases-1/3 in the murine collagen antibody-induced model of inflammatory arthritis.
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pubmed:affiliation |
Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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