Document Detail


Mannose-binding lectin-associated serine protease-1 is a significant contributor to coagulation in a murine model of occlusive thrombosis.
MedLine Citation:
PMID:  22156595     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Bleeding disorders and thrombotic complications constitute a major cause of death and disability worldwide. Although it is known that the complement and coagulation systems interact, no studies have investigated the specific role or mechanisms of lectin-mediated coagulation in vivo. FeCl(3) treatment resulted in intra-arterial occlusive thrombogenesis within 10 min in wild-type (WT) and C2/factor B-null mice. In contrast, mannose-binding lectin (MBL)-null and MBL-associated serine protease (MASP)-1/-3 knockout (KO) mice had significantly decreased FeCl(3)-induced thrombogenesis. Reconstitution with recombinant human (rh) MBL restored FeCl(3)-induced thrombogenesis in MBL-null mice to levels comparable to WT mice, suggesting a significant role of the MBL/MASP complex for in vivo coagulation. Additionally, whole blood aggregation demonstrated increased MBL/MASP complex-dependent platelet aggregation. In vitro, MBL/MASP complexes were captured on mannan-coated plates, and cleavage of a chromogenic thrombin substrate (S2238) was measured. We observed no significant differences in S2238 cleavage between WT, C2/factor B-null, MBL-A(-/-), or MBL-C(-/-) sera; however, MBL-null or MASP-1/-3 KO mouse sera demonstrated significantly decreased S2238 cleavage. rhMBL alone failed to cleave S2238, but cleavage was restored when rMASP-1 was added to either MASP-1/-3 KO sera or rhMBL. Taken together, these findings indicate that MBL/MASP complexes, and specifically MASP-1, play a key role in thrombus formation in vitro and in vivo.
Authors:
Laura R La Bonte; Vasile I Pavlov; Ying S Tan; Kazue Takahashi; Minoru Takahashi; Nirmal K Banda; Chenhui Zou; Teizo Fujita; Gregory L Stahl
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-12-12
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  188     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-06     Completed Date:  2012-02-21     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  885-91     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Coagulation* / immunology
Carotid Artery Thrombosis / chemically induced,  enzymology*,  genetics
Chlorides / toxicity
Complement Pathway, Mannose-Binding Lectin* / genetics
Disease Models, Animal
Ferric Compounds / toxicity
Humans
Immunity, Innate / genetics
Mannose-Binding Lectins / deficiency,  genetics
Mannose-Binding Protein-Associated Serine Proteases / adverse effects,  deficiency,  genetics,  physiology*
Mice
Thrombin / physiology
Grant Support
ID/Acronym/Agency:
AI089781/AI/NIAID NIH HHS; F32 HL099043-01A1/HL/NHLBI NIH HHS; F32 HL099043-02/HL/NHLBI NIH HHS; F32 HL099043-03/HL/NHLBI NIH HHS; HL056086/HL/NHLBI NIH HHS; HL099043/HL/NHLBI NIH HHS; HL099130/HL/NHLBI NIH HHS; R01 AI089781/AI/NIAID NIH HHS; R01 AI089781-01A1/AI/NIAID NIH HHS; R01 AI089781-02/AI/NIAID NIH HHS; R01 HL056086/HL/NHLBI NIH HHS; R01 HL056086-14A2/HL/NHLBI NIH HHS; R01 HL056086-15/HL/NHLBI NIH HHS; R56 AI089781/AI/NIAID NIH HHS; R56 AI089781-01/AI/NIAID NIH HHS; R56 HL056086/HL/NHLBI NIH HHS; R56 HL056086-14/HL/NHLBI NIH HHS; RC1 HL099130/HL/NHLBI NIH HHS; RC1 HL099130-02/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Chlorides; 0/Ferric Compounds; 0/Mannose-Binding Lectins; EC 3.4.21.-/MASP-2 protein, mouse; EC 3.4.21.-/MASP-3 protein, mouse; EC 3.4.21.-/Mannose-Binding Protein-Associated Serine Proteases; EC 3.4.21.5/Thrombin; U38V3ZVV3V/ferric chloride
Comments/Corrections

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