Cell-cell matrix interactions in induced lung injury II. X-irradiation mediated changes in specific basal laminar glycosaminoglycans

The thoraces of male LAF1 mice were irradiated at doses of 5, 9, or 13 Gy. The animals were killed at times of 1 hr, 1 day, 1 wk, 4 wks, and 12 wks postirradiation (PI). The lungs were removed, enzymatically or detergent digested, fixed with ruthenium red for demonstration of anionic sites, and processed for electron microscopy. Untreated (0 Gy, 0 time) and sham irradiated control groups were also processed. Sections of lungs were examined and changes in alveolar basal laminar anionic sites were quantitated. Changes in three groups of glycosaminoglycans (GAGs) were identified: chondroitin 4 and 6 sulfate-dermatan sulfate, hyaluronate, and other GAGs (principally heparan sulfate). At 1 hr PI, all groups showed a marked decrease in site number over controls, which continued to 1 wk. By 4 wks there was a marked relative increase in heparan sulfate containing sites for doses of 13 Gy and a moderate increase for the other doses. At 12 wks the level of heparan sulfate was considerably above normal for doses of 13 Gy and just above normal for the other doses. Chondroitindermatan sulfate had recovered by 12 wks for doses of 13 Gy, but was still subnormal for other doses; however, hyaluronate-containing sites recovered only slightly by 12 wks. The implications for this change on basal laminar permeability and the induction of fibrosis are discussed.