Cell-Cell Matrix Interactions in Induced Lung Injury: IV. Quantitative Alterations in Pulmonary Fibronectin and Laminin Following X Irradiation

Male LAF/1 mice were locally irradiated at doses of 5, 9, and 13 Gy and compared with untreated and sham-irradiated animals. Lungs were subsequently examined at times of 1, 4, 13, 28, 41, and 63 weeks postirradiation (PI) for alterations in pulmonary fibronectin (Fbn) and laminin (Lam) as a consequence of the irradiation. Thoroughly perfused lungs dissected clear of major airways were homogenized and fractionated by centrifugation into two fractions, soluble (supernate) and insoluble (pellet). Each fraction was analyzed by nonequilibrium competitive enzyme-linked immunoassay (ELISA) for Fbn and Lam normalized to mg protein. The results show a dose-related increase in soluble Fbn demonstrable at 1 week PI and approaching seven times control values by 28 weeks for doses of 13 Gy. Thereafter amounts decrease steadily to 63 weeks. Insoluble Fbn remains at or near control values through 13 weeks, increases in a dose-related fashion almost fivefold by 41 weeks for doses of 13 Gy, and then decreases by 63 weeks. Soluble Lam increased slightly during the duration of the study, returning to normal by 63 weeks. Insoluble Lam shows a dose-dependent increase demonstrable at 4 weeks PI which continues through 63 weeks. Interactions between these alterations in Fbn and Lam and previously reported changes in basal laminar proteoglycans may, in concert with other cellular and extracellular components, relate to the initiation and/or maintenance of radiation-induced pulmonary fibrosis.