Lung Hyperpermeability and Changes in Biochemical Constituents in Bronchoalveolar Lavage Fluids Following X Irradiation of the Thorax

Abstract

Groups of rats were administered different doses of X rays (7.5 and 15 Gy), and the effect on the permeability of their lungs was evaluated during a time frame within which radiation pneumonitis develops. Sham-exposed animals served as controls. End points surveyed included lung weight and increases in the total protein in the lavage fluid. To obtain more detailed information about hyperpermeability and to examine some specific protein changes that occur in the lung's fluid in response to X irradiation, the lavage fluids were subjected to a reverse-phase HPLC technique that resolves 11 fractions quantitatively, including transferrin, albumin, and immunoglobulins derived from blood, as well as eight other protein and nonprotein constituents that appear to be derived from the lung (fractions 1, 2, 6-11). The earliest change following the 7.5-Gy dose was a decrease in fraction 6 at 1 week after exposure. As of Week 5, the lung weight and total protein in the lavage fluid were all normal, while the HPLC analyses revealed significant and equivalent increases in the amount of transferrin, albumin, and immunoglobulins in the lavage fluid; fraction 6 was no longer diminished. At 9 and 13 weeks, hyperpermeability could no longer be detected, while fraction 6 was again decreased at week 13. Fraction 6 was also decreased 1 week after the 15-Gy dose. At 5 weeks, when the weight of the lungs and the total protein in the lavage fluid were elevated, lavage fractions 1, 2, 10, and 11 were all increased, and transferrin, albumin, and immunoglobulins were increased approximately 1500, 1000, and 500%, respectively, and fractions 6 and 9 were decreased. By Week 7, the weight of the lungs returned to control limits, while total protein in the lavage fluid remained elevated. The hyperpermeability was characterized by increases in transferrin and albumin in the lavage fluid, but not immunoglobulins. Fractions 1, 2, 10, and 11 returned to within normal limits, whereas fraction 9 decreased further. Increases in transferrin and albumin were components of a persisting hyperpermeability observed at the last 9-week time point. All other fractions were normal, with the exception of fraction 6, which remained decreased.(ABSTRACT TRUNCATED AT 400 WORDS)

Radiation-Induced Lung Injury—Current Perspectives and Management

“…Type 1 pneumocytes are terminally differentiated and are often not affected by irradiation. In a rat model exposed to different doses of X-rays, within a few hours of irradiation the lungs became hyperpermeable due to damage to type II pneumocytes and developed increased surfactant production visible on electron microscopy, which would predispose to the risk of pneumonitis [ 13 ].…”

“…The lymphocyte count is generally elevated with inflammatory conditions; an irradiated lung shows elevated activated neutrophils, eosinophils, and macrophages. It is not necessarily performed to diagnose RP but to rule out other causes like infection, bleeding, or local spread of the tumor cells [ 13 ].…”

The Acute Inhalation Toxicity of Pyrolysis Products of Halon 1301: Kinetic Course of Lung Injury, Degradation in Work Performance, and Exercise Potentiation of Lung Injury after Phosgene Exposure

“…(25) and bovine serum albumin as a protein standard. This biochemical parameter was used as an index of the amount of transudation of serum proteins into the alveoli because of damage to the alveolar-capillary barrier (26,27). As previously reported by others (28), abnormal increases in protein in lavage fluid following phosgene exposure has been shown to be a more sensitive indicator of lung damage than are lung gravimetric increases and lung histopathologic changes.…”