Polymerization of fibrinogen in murine bleomycin-induced lung
injury.
Olman, Mitchell A., Warren L. Simmons, Daniel J. Pollman, Audrey Y.
Loftis, Alessandra Bini, Edward J. Miller, Gerald. M. Fuller, and
Kimberly E. Rivera.
Division of Pulmonary and Critical Care Medicine and the
Departments of Pathology, Biochemistry and Molecular Genetics and
Cell Biology at the University of Alabama, Birmingham AL, 35294 and
The New York Blood Center, Laboratory of Blood Coagulation
Biochemistry, New York, NY, 10021
APStracts 3:0065L, 1996.
Bleomycin lung injury in mice leads to an acute alveolitis followed by
a fibroproliferative response characterized by the accumulation of
extracellular matrix. As distinct regions of the fibrin(ogen)
molecule have unique in vitro biological effects on cells, we
quantified, localized and biochemically characterized the molecular
form of extravascular fibrin(ogen) in methoxyflurane anesthetized,
bleomycin-injured mice. Bleomycin or saline (controls) were
administered intratracheally, and lung tissue was harvested and
analyzed at several times thereafter. Immunoreactive fibrin tissue
content increased to a maximal 50 fold over controls, in a temporal
and spatial pattern paralleling that of alveolitis and maximal
fibroproliferation. The generation of [delta]-[delta] chain dimers
and [alpha]- chain polymers together with the loss of free [alpha]
and [delta] chains indicates that the fibrin is predominantly
covalently cross-linked. In fibroproliferative phase lungs, the
fibrin fibrils are branched and co-localize with those of collagen at
the electron microscopic level. These observations strongly suggest
that fibrin is a significant molecular effector of the in vivo
fibroproliferative response after lung injury.
Received 10 January 1996; accepted in final form 22 April 1996.
APS Manuscript Number L10-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96