Lessons learned from mice deficient in lectin complement pathway molecules

TY - JOUR

T1 - Lessons learned from mice deficient in lectin complement pathway molecules

AU - Genster, Ninette

AU - Takahashi, Minoru

AU - Sekine, Hideharu

AU - Endo, Yuichi

AU - Garred, Peter

AU - Fujita, Teizo

N1 - Copyright © 2014 Elsevier Ltd. All rights reserved.

PY - 2014/10

Y1 - 2014/10

N2 - The lectin pathway of the complement system is initiated when the pattern-recognition molecules, mannose-binding lectin (MBL), ficolins or collectin-11, bind to invading pathogens or damaged host cells. This leads to activation of MBL/ficolin/collectin-11 associated serine proteases (MASPs), which in turn activate downstream complement components, ultimately leading to elimination of the pathogen. Mice deficient in the key molecules of lectin pathway of complement have been generated in order to build knowledge of the molecular mechanisms of the lectin pathway in health and disease. Despite differences in the genetic arrangements of murine and human orthologues of lectin pathway molecules, the knockout mice have proven to be valuable models to explore the effect of deficiency states in humans. In addition, new insight and unexpected findings on the diverse roles of lectin pathway molecules in complement activation, pathogen infection, coagulation, host tissue injury and developmental biology have been revealed by in vivo investigations. This review provides an overview of the mice deficient in lectin pathway molecules and highlights some of the most important findings that have resulted from studies of these.

AB - The lectin pathway of the complement system is initiated when the pattern-recognition molecules, mannose-binding lectin (MBL), ficolins or collectin-11, bind to invading pathogens or damaged host cells. This leads to activation of MBL/ficolin/collectin-11 associated serine proteases (MASPs), which in turn activate downstream complement components, ultimately leading to elimination of the pathogen. Mice deficient in the key molecules of lectin pathway of complement have been generated in order to build knowledge of the molecular mechanisms of the lectin pathway in health and disease. Despite differences in the genetic arrangements of murine and human orthologues of lectin pathway molecules, the knockout mice have proven to be valuable models to explore the effect of deficiency states in humans. In addition, new insight and unexpected findings on the diverse roles of lectin pathway molecules in complement activation, pathogen infection, coagulation, host tissue injury and developmental biology have been revealed by in vivo investigations. This review provides an overview of the mice deficient in lectin pathway molecules and highlights some of the most important findings that have resulted from studies of these.

KW - Animals

KW - Complement Pathway, Mannose-Binding Lectin

KW - Humans

KW - Lectins

KW - Mannose-Binding Lectins

KW - Mannose-Binding Protein-Associated Serine Proteases

KW - Mice

KW - Mice, Knockout

U2 - 10.1016/j.molimm.2014.07.007

DO - 10.1016/j.molimm.2014.07.007

M3 - Journal article

C2 - 25060538

SN - 0161-5890

VL - 61

SP - 59

EP - 68

JO - Molecular Immunology

JF - Molecular Immunology

IS - 2

ER -