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.
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.
Takahashi
Kazue
K
Developmental Immunology Program, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. ktakahashi1@partners.org
Chang
Wei-Chuan
WC
Takahashi
Minoru
M
Pavlov
Vasile
V
Ishida
Yumi
Y
La Bonte
Laura
L
Shi
Lei
L
Fujita
Teizo
T
Stahl
Gregory L
GL
Van Cott
Elizabeth M
EM
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
D015850:Interleukin-6; D037601:Mannose-Binding Lectin; D050606:Mannose-Binding Protein-Associated Serine Proteases; D013917:Thrombin
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