Experimental radiation pneumonitis. IV. Leakage of circulatory proteins onto the alveolar surface.

We have previously shown that the fall in lung compliance in radiation pneumonitis is mainly due to abnormality of the alveolar surface lining layer and speculated that this, in turn, is due to an increased amount of protein in the alveolar lining fluid layer. In the present study, this extra protein has been partially characterized, and the kinetics of permeation from the blood to the lung and the AF have been investigated by using intravenously injected of 125I-labeled albumin. Mice which had received 3000 rads to the thorax were used. A fourfold to fivefold increase in the total protein in AF obtained by pulmonary lavage was again found in mice irradiated 4 months previously, as compared to control littermates. With immunologic techniques and polyacrylamide disc-gel electrophoresis the excess protein in the alveolar lavage fluid was shown to be derived from the circulation. Following injection of 125I-labeled albumin into the tail vein, APR in the perfused, lavaged lung relative to radioactivity in simultaneously obtained blood rose to a plateau at 6 hr, which was approximately twice as high in irradiated mice as in controls. APR in the AF relative to that in simultaneously obtained blood rose rapidly and continued to rise throughout the period of study, reaching a level which was six times that in control mice at 24 hr. A major abnormality in radiation pneumonitis appears to be a large increase in permeability of the capillary and alveolar membranes to both small and large protein molecules. These abnormalities are not acute terminal events but probably persist for some weeks before death. It is speculated that leakage of plasma proteins onto the alveolar surface is responsible for the fall in compliance of the AF lining layer in radiation pneumonitis.