Effect of macrophage and matrix metalloproteinase-9 on proliferation of pulmonary fibroblast and synthesis of collagen IV

Objective To explore pathogenetic mechanism in initiation of radiation-induced pulmonary fibrosis. Methods Alveolar macrophages in Wistar rats irradiated by ~ 60 Co γ-ray were collected by alveolar lavage; condition medium was prepared for stimulating human lung fibroblast (HLF) proliferation; HLF proliferation activity was determined by MTT method; collagen Ⅳ (Col Ⅳ) in HLF was determined by Western blot; the activity of matrix metalloproteinase-9 (MMP-9) was determined by zymography. Results HLF proliferation activity was significantly increased after stimulation of condition medium, and the increase was most evident within 48-72 hs. Col Ⅳ synthesis in HLF was increased and reached a peak at 12 h after stimulation and then began to decrease. MMP-9 activity began to increase at 12 h and reached a peak at 48 h and then decreased after 72 h. Conclusions Cobalt-60 gamma ray irradiation of 20 Gy can stimulate secretion of some cytokines in alveolar macrophage to promote pulmonary interstitial fibroblast proliferation and synthesis of Col Ⅳ. Col Ⅳ can stimulate MMP-9 increase; MMP-9 can degrade excess Col Ⅳ. Such changes are involved in remodeling process of early pulmonary injury. ;