Fibrinogen as a key regulator of inflammation in disease

Semin Immunopathol. 2012 Jan;34(1):43-62. doi: 10.1007/s00281-011-0290-8. Epub 2011 Oct 31.

Abstract

The interaction of coagulation factors with the perivascular environment affects the development of disease in ways that extend beyond their traditional roles in the acute hemostatic cascade. Key molecular players of the coagulation cascade like tissue factor, thrombin, and fibrinogen are epidemiologically and mechanistically linked with diseases with an inflammatory component. Moreover, the identification of novel molecular mechanisms linking coagulation and inflammation has highlighted factors of the coagulation cascade as new targets for therapeutic intervention in a wide range of inflammatory human diseases. In particular, a proinflammatory role for fibrinogen has been reported in vascular wall disease, stroke, spinal cord injury, brain trauma, multiple sclerosis, Alzheimer's disease, rheumatoid arthritis, bacterial infection, colitis, lung and kidney fibrosis, Duchenne muscular dystrophy, and several types of cancer. Genetic and pharmacologic studies have unraveled pivotal roles for fibrinogen in determining the extent of local or systemic inflammation. As cellular and molecular mechanisms for fibrinogen functions in tissues are identified, the role of fibrinogen is evolving from a marker of vascular rapture to a multi-faceted signaling molecule with a wide spectrum of functions that can tip the balance between hemostasis and thrombosis, coagulation and fibrosis, protection from infection and extensive inflammation, and eventually life and death. This review will discuss some of the main molecular links between coagulation and inflammation and will focus on the role of fibrinogen in inflammatory disease highlighting its unique structural properties, cellular targets, and signal transduction pathways that make it a potent proinflammatory mediator and a potential therapeutic target.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / immunology
  • Alzheimer Disease / metabolism
  • Animals
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism
  • Bacterial Infections / genetics
  • Bacterial Infections / immunology
  • Bacterial Infections / metabolism
  • Blood Coagulation / genetics
  • Blood Coagulation / immunology*
  • Brain Injuries / genetics
  • Brain Injuries / immunology
  • Brain Injuries / metabolism
  • Colitis / genetics
  • Colitis / immunology
  • Colitis / metabolism
  • Fibrinogen / genetics
  • Fibrinogen / immunology*
  • Fibrinogen / metabolism
  • Humans
  • Inflammation / genetics
  • Inflammation / immunology*
  • Inflammation / metabolism
  • Kidney Diseases / genetics
  • Kidney Diseases / immunology
  • Kidney Diseases / metabolism
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / metabolism
  • Muscular Dystrophy, Duchenne / genetics
  • Muscular Dystrophy, Duchenne / immunology
  • Muscular Dystrophy, Duchenne / metabolism
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Pulmonary Fibrosis / genetics
  • Pulmonary Fibrosis / immunology
  • Pulmonary Fibrosis / metabolism
  • Spinal Cord Injuries / genetics
  • Spinal Cord Injuries / immunology
  • Spinal Cord Injuries / metabolism
  • Stroke / genetics
  • Stroke / immunology
  • Stroke / metabolism
  • Thrombin / genetics
  • Thrombin / immunology
  • Thrombin / metabolism
  • Thromboplastin / genetics
  • Thromboplastin / immunology
  • Thromboplastin / metabolism
  • Vascular Diseases / genetics
  • Vascular Diseases / immunology
  • Vascular Diseases / metabolism

Substances

  • Fibrinogen
  • Thromboplastin
  • Thrombin