Fukuda Y, Ferrans V J, Schoenberger C I, Rennard S I, Crystal R G
Am J Pathol. 1985 Mar;118(3):452-75.
For a study of the evolution of interstitial and intraalveolar fibrosis, ultrastructural and immunohistochemical observations were made of the lungs of 16 cynomolgous monkeys given 1 or 2 injections of 10 mg/kg of paraquat and sacrificed 2 days to 8 weeks later. At 2-3 days, alveolar epithelial cells were denuded in many areas, and fibronectin was conspicuous in alveolar spaces. At 1 week, fibroblasts and inflammatory cells were migrating through gaps in the denuded epithelial basement membranes; Type II cells were regenerating in some areas. At 3-4 weeks, alveoli developing intraalveolar fibrosis contained many myofibroblasts, collagen fibrils, and small elastic fibers; fibrotic alveolar walls were lined by metaplastic squamous cells and bronchiolar epithelial cells. Spiraling collagen fibrils were found in interstitium but not in alveolar spaces, which suggests that they were formed from breakdown of collagen. Newly formed intraalveolar collagen was mainly Type I. At 8 weeks, intraalveolar fibrosis had led to extensive remodeling, with new glandlike alveoli lined by Type II cells; alveoli without intraalveolar fibrosis had more normal architecture. Thus, intraalveolar fibrosis in paraquattreated lung is mediated by intraalveolar migration of interstitial cells, through gaps in the epithelial basement membranes, after epithelial injury. This is followed by connective tissue synthesis on the luminal side of the epithelial basement membrane, by differentiation of interstitial cells into myofibroblasts and smooth-muscle cells, by incorporation of areas of intraalveolar fibrosis into the interstitium, and by coalescence of alveolar walls. Intraalveolar fibrosis is more important than interstitial fibrosis in the structural remodeling that occurs in paraquattreated lung, because it results in obliteration of alveoli, coalescence of alveolar walls, and loss of functional alveolar-capillary units.
为研究间质性和肺泡内纤维化的演变，对16只食蟹猴的肺进行了超微结构和免疫组织化学观察。这些食蟹猴接受了1或2次10mg/kg百草枯注射，并于2天至8周后处死。在2 - 3天时，许多区域的肺泡上皮细胞剥脱，肺泡腔内纤连蛋白明显。在1周时，成纤维细胞和炎性细胞通过剥脱的上皮基底膜间隙迁移；部分区域Ⅱ型细胞再生。在3 - 4周时，发生肺泡内纤维化的肺泡含有许多肌成纤维细胞、胶原纤维和小弹性纤维；纤维化的肺泡壁由化生的鳞状细胞和细支气管上皮细胞衬里。在间质中发现螺旋状胶原纤维，但肺泡腔内未发现，这表明它们是由胶原分解形成的。新形成的肺泡内胶原主要为Ⅰ型。在8周时，肺泡内纤维化导致广泛重塑，新的腺泡样肺泡由Ⅱ型细胞衬里；无肺泡内纤维化的肺泡结构更正常。因此，百草枯处理的肺中肺泡内纤维化是由间质细胞在肺泡上皮损伤后通过上皮基底膜间隙向肺泡内迁移介导的。随后，在上皮基底膜腔面进行结缔组织合成，间质细胞分化为肌成纤维细胞和平滑肌细胞，肺泡内纤维化区域并入间质，肺泡壁融合。在百草枯处理的肺发生的结构重塑中，肺泡内纤维化比间质性纤维化更重要，因为它导致肺泡闭塞、肺泡壁融合以及功能性肺泡 - 毛细血管单位丧失。
