The procoagulant and proinflammatory plasma contact system.

TY - JOUR

T1 - The procoagulant and proinflammatory plasma contact system.

AU - Renné, Thomas

PY - 2012

Y1 - 2012

N2 - The contact system is a plasma protease cascade that is initiated by coagulation factor XII activation on cardiovascular cells. The system starts procoagulant and proinflammatory reactions, via the intrinsic pathway of coagulation or the kallikrein-kinin system, respectively. The biochemistry of the contact system in vitro is well understood, however, its in vivo functions are just beginning to emerge. Data obtained in genetically engineered mice have revealed an essential function of the contact system for thrombus formation. Severe deficiency in contact system proteases impairs thrombus formation but does not reduce the hemostatic capacity of affected individuals. The system is activated by an inorganic polymer, polyphosphate that is released from activated platelets. Excessive inherited activation of the contact system causes a life-threatening swelling disorder, hereditary angioedema. Activation of the contact system by pathogens contributes to leakage in bacterial infections. Mast-cell-derived heparin triggers contact-system-mediated edema formation with implications for allergic disease states. Here we present an overview about the plasma contact system in occlusive and inflammatory disease and its contribution to health and pathology.

AB - The contact system is a plasma protease cascade that is initiated by coagulation factor XII activation on cardiovascular cells. The system starts procoagulant and proinflammatory reactions, via the intrinsic pathway of coagulation or the kallikrein-kinin system, respectively. The biochemistry of the contact system in vitro is well understood, however, its in vivo functions are just beginning to emerge. Data obtained in genetically engineered mice have revealed an essential function of the contact system for thrombus formation. Severe deficiency in contact system proteases impairs thrombus formation but does not reduce the hemostatic capacity of affected individuals. The system is activated by an inorganic polymer, polyphosphate that is released from activated platelets. Excessive inherited activation of the contact system causes a life-threatening swelling disorder, hereditary angioedema. Activation of the contact system by pathogens contributes to leakage in bacterial infections. Mast-cell-derived heparin triggers contact-system-mediated edema formation with implications for allergic disease states. Here we present an overview about the plasma contact system in occlusive and inflammatory disease and its contribution to health and pathology.

KW - Animals

KW - Humans

KW - Mice

KW - Mice, Transgenic

KW - Angioedemas, Hereditary/genetics/immunology

KW - Bacterial Infections/genetics/immunology

KW - Blood Coagulation/genetics/immunology

KW - Blood Platelets/immunology

KW - Factor XII/genetics/immunology

KW - Hypersensitivity/genetics/immunology

KW - Inflammation/genetics/immunology

KW - Kallikreins/genetics/immunology

KW - Kinins/genetics/immunology

KW - Plasma/immunology

KW - Platelet Activation/immunology

KW - Thrombosis/genetics/immunology

KW - Animals

KW - Humans

KW - Mice

KW - Mice, Transgenic

KW - Angioedemas, Hereditary/genetics/immunology

KW - Bacterial Infections/genetics/immunology

KW - Blood Coagulation/genetics/immunology

KW - Blood Platelets/immunology

KW - Factor XII/genetics/immunology

KW - Hypersensitivity/genetics/immunology

KW - Inflammation/genetics/immunology

KW - Kallikreins/genetics/immunology

KW - Kinins/genetics/immunology

KW - Plasma/immunology

KW - Platelet Activation/immunology

KW - Thrombosis/genetics/immunology

M3 - SCORING: Journal article

VL - 34

SP - 31

EP - 41

JO - SEMIN IMMUNOPATHOL

JF - SEMIN IMMUNOPATHOL

SN - 1863-2297

IS - 1

M1 - 1

ER -