title: 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.
abstract: 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.affiliation: Developmental Immunology Program, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. ktakahashi1@partners.org
authors.forename: Kazue
authors.initials: K
authors.lastname: Takahashi
authors.forename: Wei-Chuan
authors.initials: WC
authors.lastname: Chang
authors.forename: Minoru
authors.initials: M
authors.lastname: Takahashi
authors.forename: Vasile
authors.initials: V
authors.lastname: Pavlov
authors.forename: Yumi
authors.initials: Y
authors.lastname: Ishida
authors.forename: Laura
authors.initials: L
authors.lastname: La Bonte
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Teizo
authors.initials: T
authors.lastname: Fujita
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Stahl
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Van Cott
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001777:Blood Coagulation / Q000235:genetics; D037582:Complement Pathway, Mannose-Binding Lectin / Q000235:genetics; D004198:Disease Susceptibility; D004211:Disseminated Intravascular Coagulation / Q000453:epidemiology / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D037601:Mannose-Binding Lectin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012307:Risk Factors; D013203:Staphylococcal Infections / Q000453:epidemiology / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D013211:Staphylococcus aureus / Q000276:immunology* / Q000472:pathogenicity; D013917:Thrombin / Q000276:immunology / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D037601:Mannose-Binding Lectin; D050606:Mannose-Binding Protein-Associated Serine Proteases; D013917:Thrombin
references.citation: Clin Infect Dis. 2005 Nov 15;41 Suppl 7:S440-4
references.pmid: 16237644
references.citation: J Immunol. 2008 May 1;180(9):6132-8
references.pmid: 18424734
references.citation: Thromb Haemost. 2007 Sep;98(3):503-11
references.pmid: 17849038
references.citation: J Intern Med. 2005 Feb;257(2):122-5
references.pmid: 15656871
references.citation: J Immunol. 2000 Mar 1;164(5):2610-8
references.pmid: 10679100
references.citation: J Clin Invest. 1999 Aug;104(4):431-7
references.pmid: 10449435
references.citation: J Immunol. 2005 Jul 1;175(1):541-6
references.pmid: 15972690
references.citation: Biochim Biophys Acta. 2008 Sep;1784(9):1294-300
references.pmid: 18456010
references.citation: Intensive Care Med. 2003 Jan;29(1):55-61
references.pmid: 12528023
references.citation: Mol Immunol. 2004 Feb;40(13):921-9
references.pmid: 14725788
references.citation: J Cell Physiol. 1992 Nov;153(2):321-31
references.pmid: 1429852
references.citation: J Biol Chem. 1993 May 15;268(14):10120-5
references.pmid: 8486682
references.citation: Adv Exp Med Biol. 2007;598:93-104
references.pmid: 17892207
references.citation: Leuk Lymphoma. 2004 Feb;45(2):247-56
references.pmid: 15101708
references.citation: Blood. 2002 Oct 1;100(7):2522-9
references.pmid: 12239165
references.citation: Mol Immunol. 2004 Jun;41(2-3):103-11
references.pmid: 15159055
references.citation: J Immunol. 2009 Sep 1;183(5):3409-16
references.pmid: 19667088
references.citation: Lancet. 1991 Jun 29;337(8757):1569-70
references.pmid: 1675710
references.citation: Clin Lab Haematol. 2002 Dec;24(6):321-7
references.pmid: 12452811
references.citation: Thromb Haemost. 1998 Jul;80(1):65-9
references.pmid: 9684787
references.citation: J Exp Med. 2004 May 17;199(10):1379-90
references.pmid: 15148336
references.citation: Clin Exp Immunol. 2007 Apr;148(1):101-5
references.pmid: 17286761
references.citation: EMBO J. 2007 Jul 25;26(14):3431-40
references.pmid: 17581635
references.citation: J Immunol. 2006 Dec 15;177(12):8626-32
references.pmid: 17142762
references.citation: Nature. 1997 Nov 13;390(6656):172-5
references.pmid: 9367154
references.citation: Immunobiology. 2004;209(7):559-68
references.pmid: 15568620
references.citation: Clin Exp Immunol. 1997 Nov;110(2):317-23
references.pmid: 9367419
references.citation: Prog Mol Subcell Biol. 1996;15:154-89
references.pmid: 8963461
references.citation: Scand J Immunol. 2007 May;65(5):430-4
references.pmid: 17444953
references.citation: J Exp Med. 2008 Jan 21;205(1):169-81
references.pmid: 18180310
references.citation: J Immunol. 2006 Feb 1;176(3):1769-75
references.pmid: 16424207
references.citation: J Immunol. 2002 Dec 15;169(12):6945-50
references.pmid: 12471128
references.citation: Mol Immunol. 2003 Sep;40(2-4):73-84
references.pmid: 12914814
references.citation: J Immunol. 1998 Sep 15;161(6):3169-75
references.pmid: 9743385
references.citation: Crit Care Med. 2004 Dec;32(12):2416-21
references.pmid: 15599145
references.citation: Nephron Clin Pract. 2006;102(3-4):c93-9
references.pmid: 16282701
references.citation: Curr Opin Immunol. 2006 Feb;18(1):16-23
references.pmid: 16368230
references.citation: J Exp Med. 1994 Apr 1;179(4):1253-9
references.pmid: 8145042
references.citation: Crit Care Med. 2005 Feb;33(2):341-8
references.pmid: 15699837
references.citation: J Immunol. 2006 Apr 1;176(7):4369-74
references.pmid: 16547275
references.citation: Am J Clin Pathol. 2004 Jan;121(1):138-41
references.pmid: 14750251
references.citation: Clin Exp Immunol. 2004 Nov;138(2):304-11
references.pmid: 15498041
references.citation: J Immunol. 2003 Feb 1;170(3):1374-82
references.pmid: 12538697
references.citation: J Immunol. 2000 Sep 1;165(5):2637-42
references.pmid: 10946292
references.citation: Infect Immun. 2005 Dec;73(12):8188-93
references.pmid: 16299314
references.citation: Lab Invest. 1982 Jul;47(1):60-6
references.pmid: 6177923
references.citation: Immunobiology. 2002 Sep;205(4-5):467-75
references.pmid: 12396008
references.citation: PLoS One. 2007 Jul 18;2(7):e623
references.pmid: 17637839
references.citation: Am J Pathol. 2002 May;160(5):1867-75
references.pmid: 12000738
references.citation: Immunobiology. 2007;212(4-5):289-99
references.pmid: 17544814
references.citation: Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13519-24
references.pmid: 11707569
references.citation: Microb Pathog. 2001 Apr;30(4):247-52
references.pmid: 11312618
references.citation: J Biol Chem. 2004 Nov 12;279(46):47513-9
references.pmid: 15331601
references.citation: Hybrid Hybridomics. 2002 Feb;21(1):25-36
references.pmid: 11991814
references.citation: Trends Cardiovasc Med. 2005 Oct;15(7):254-9
references.pmid: 16226680
references.citation: J Immunol Methods. 2000 Jul 31;241(1-2):33-42
references.pmid: 10915847
references.citation: Genes Immun. 2006 Mar;7(2):85-94
references.pmid: 16395391