Document Detail


Mannose-binding lectin and its associated proteases (MASPs) mediate coagulation and its deficiency is a risk factor in developing complications from infection, including disseminated intravascular coagulation.
MedLine Citation:
PMID:  20399528     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The first line of host defense is the innate immune system that includes coagulation factors and pattern recognition molecules, one of which is mannose-binding lectin (MBL). Previous studies have demonstrated that MBL deficiency increases susceptibility to infection. Several mechanisms are associated with increased susceptibility to infection, including reduced opsonophagocytic killing and reduced lectin complement pathway activation. In this study, we demonstrate that MBL and MBL-associated serine protease (MASP)-1/3 together mediate coagulation factor-like activities, including thrombin-like activity. MBL and/or MASP-1/3 deficient hosts demonstrate in vivo evidence that MBL and MASP-1/3 are involved with hemostasis following injury. Staphylococcus aureus infected MBL null mice developed disseminated intravascular coagulation (DIC), which was associated with elevated blood IL-6 levels (but not TNF-α and multi-organ inflammatory responses). Infected MBL null mice also develop liver injury. These findings suggest that MBL deficiency may manifest into DIC and organ failure during infectious diseases.
Authors:
Kazue Takahashi; Wei-Chuan Chang; Minoru Takahashi; Vasile Pavlov; Yumi Ishida; Laura La Bonte; Lei Shi; Teizo Fujita; Gregory L Stahl; Elizabeth M Van Cott
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-03-04
Journal Detail:
Title:  Immunobiology     Volume:  216     ISSN:  1878-3279     ISO Abbreviation:  Immunobiology     Publication Date:    2011 Jan-Feb
Date Detail:
Created Date:  2010-11-29     Completed Date:  2011-07-18     Revised Date:  2012-01-04    
Medline Journal Info:
Nlm Unique ID:  8002742     Medline TA:  Immunobiology     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  96-102     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier GmbH. All rights reserved.
Affiliation:
Developmental Immunology Program, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. ktakahashi1@partners.org
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MeSH Terms
Descriptor/Qualifier:
Adoptive Transfer
Animals
Blood Coagulation / genetics
Complement Pathway, Mannose-Binding Lectin / genetics
Disease Susceptibility
Disseminated Intravascular Coagulation / epidemiology,  genetics,  immunology*,  physiopathology
Interleukin-6 / genetics,  metabolism
Liver / immunology,  metabolism,  microbiology,  pathology
Mannose-Binding Lectin / genetics,  immunology,  metabolism*
Mannose-Binding Protein-Associated Serine Proteases / genetics,  immunology,  metabolism*
Mice
Mice, Inbred C57BL
Mice, Knockout
Risk Factors
Staphylococcal Infections / epidemiology,  genetics,  immunology*,  physiopathology
Staphylococcus aureus / immunology*,  pathogenicity
Thrombin / immunology,  metabolism
Grant Support
ID/Acronym/Agency:
R01HL52886/HL/NHLBI NIH HHS; R01HL56086/HL/NHLBI NIH HHS; R21 AI077081-01/AI/NIAID NIH HHS; R21 AI077081-02/AI/NIAID NIH HHS; R21AI077081/AI/NIAID NIH HHS; R21HL092469/HL/NHLBI NIH HHS; R56HL056086/HL/NHLBI NIH HHS; RC1HL099130/HL/NHLBI NIH HHS; U01 AI074503/AI/NIAID NIH HHS; U01 AI074503-01/AI/NIAID NIH HHS; U01 AI074503-02/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Interleukin-6; 0/Mannose-Binding Lectin; EC 3.4.21.-/Mannose-Binding Protein-Associated Serine Proteases; EC 3.4.21.5/Thrombin

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