Dynamic changes in protein biomarkers of alveolar-capillary barrier disruption in phosgene-induced pulmonary edema: a comparative analysis of plasma and bronchoalveolar lavage fluid in mice
PATHOPHYSIOLOGY — MEDICINE
Abstract
Introduction.The key pathogenetic mechanism of toxic pulmonary edema is increased permeability of the aerohematic barrier to the liquid portion of the blood and proteins, the pathognomonic sign of which is an increase in the protein content in the exudate and, consequently, in the lavage fluid.The aim of the studywas to evaluate the dynamics of the content and fractional composition of proteins in bronchoalveolar lavage and blood plasma in mice with toxic pulmonary edema induced by inhalation of carbonic acid dichloride.Materials and methods.The study was performed on non-inbred male mice weighing 18–24 g. Toxic pulmonary edema was induced by inhalation static poisoning of the animals with carbonic acid dichloride in a chamber at a dose corresponding to LCt16-50. The development of toxic pulmonary edema was determined by the pulmonary coefficient. Total protein content in lavage fluid, as well as total protein, albumin, and globulin levels in plasma, were determined.Results.It was shown that protein content in bronchoalveolar lavage fluid increased more than 10-fold compared to control levels within 3 hours after exposure, and more than 25-fold by 24 hours. However, no changes in plasma protein composition were observed early (3 hours). After 24 hours, an increase in total plasma protein was observed due to an increase in the globulin fraction, accompanied by a decrease in albumin levels. These data indicate severe and progressive damage to the blood-air barrier, manifested within the first hours after toxic exposure, and point to the development of a systemic inflammatory response later.Conclusion.The results confirm the key role of barrier permeability impairment in the pathogenesis of toxic pulmonary edema.
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