A total fibrinogen deficiency is compatible with the development of pulmonary fibrosis in mice.

Abstract

In addition to their well-known roles in hemostasis, fibrinogen (Fg) and fibrin (Fn) have been implicated in a number of other physiological and pathophysiological events. One of these involves the fibroproliferative response after acute lung injury, which is the focus of the current study. Mice with a total Fg deficiency (FG(-/-)) were generated by breeding heterozygous (FG(+/-)) pairs, each of which contained an allele with a targeted deletion of its Fg-gamma-chain gene. The resulting FG(-/-) animals did not possess detectable plasma Fg. FG(-/-) mice were then used to assess the roles of Fg and Fn in a bleomycin-induced acute lung injury model. Intratracheal administration of bleomycin in wild-type and FG(-/-) mice resulted in equivalent deposition of interstitial collagen and fibrotic lesions at days 7 and 14 after administration. This indicates that Fg and/or Fn are not essential for the development of bleomycin-induced pulmonary fibrosis.

• Authors: V A Ploplis, J Wilberding, L McLennan, Z Liang, I Cornelissen, M E DeFord, E D Rosen, F J Castellino
• Journal: The American journal of pathology (Am J Pathol) Vol. 157 Issue 3 Pg. 703-8 (Sep 2000) ISSN: 0002-9440 [Print] United States
• PMID: 10980108 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• fibrinopeptides gamma
• Bleomycin
• Fibrinogen
• Collagen
• DNA

Topics

• Afibrinogenemia (genetics, metabolism, pathology)
• Animals
• Bleomycin
• Collagen (metabolism)
• DNA (analysis)
• Disease Models, Animal
• Female
• Fibrinogen (genetics, metabolism)
• Fluorescent Antibody Technique, Indirect
• Gene Targeting
• Heterozygote
• Homozygote
• Lung (drug effects, metabolism, pathology)
• Male
• Mice
• Mice, Knockout
• Polymerase Chain Reaction
• Pulmonary Fibrosis (chemically induced, genetics, metabolism, pathology)