Polymerization of fibrinogen in murine bleomycin-induced lung injury

MA Olman, WL Simmons, DJ Pollman… - … of Physiology-Lung …, 1996 - journals.physiology.org
MA Olman, WL Simmons, DJ Pollman, AY Loftis, A Bini, EJ Miller, GM Fuller, KE Rivera
American Journal of Physiology-Lung Cellular and Molecular …, 1996journals.physiology.org
Bleomycin lung injury in mice leads to an acute alveolitis followed by a fibroproliferative
response characterized by the accumulation of extracellular matrix. Because 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) was
administered intratracheally, and lung tissue was harvested and analyzed at several times …
Bleomycin lung injury in mice leads to an acute alveolitis followed by a fibroproliferative response characterized by the accumulation of extracellular matrix. Because 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) was 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 gamma-gamma-chain dimers and alpha-chain polymers, together with the loss of free alpha- and gamma-chains, indicates that the fibrin is predominantly covalently cross-linked. In fibroproliferative-phase lungs, the fibrin fibrils are branched and colocalize 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.
American Physiological Society