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 ∼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. Our results demonstrate: (1) the lung weight and increases in total protein in the lavage fluid used traditionally are not reliable indexes of X-irradiation-induced pulmonary hyperpermeability; (2) the hyperpermeability as a response to X rays can differ in magnitude, in its kinetic course, in its qualitative nature, and in its persistence as a function of exposure dose; and (3) numerous changes can occur in various nonplasma constituents in the lung's extracellular fluid before, during, and after the occurrence of hyperpermeability.

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