title: Morphogenesis of rat experimental pulmonary emphysema induced by intratracheally administered papain: changes in elastic fibres.
abstract: The ultrastructural changes of elastic fibres in emphysematous lungs have been studied in men, but few works exist on this topic in experimental emphysematous animals. In this paper, the morphogenesis of emphysema and alterations of the elastic fibres produced by the instillation of papain are described by light and electron microscopy. Wistar rats were instilled through the trachea with papain at a rate of 3 mg/100 g animal weight. The animals were sacrificed 12 h, 3 days, 10 days and 60 days after enzyme instillation. The "Mean Linear Intercept" (MLI), the "Number of fenestrations/respiratory units" (NF) the "Number of macrophages per mm of alveolar wall" (NM) and the "Number of respiratory unit/mm2" (RU), both in the control and experimental groups were studied. Two months after treatment, the experimental group showed a strong increase in the MLI (p<0.001) and NF (p<0.001), and a diminished number of RU (p<0.05) compared with the control group. Partial correlation analysis showed a positive correlation only between MLI and NF. Twelve hours after papain instillation an inflammatory response was observed, the elastic fibres were ruptured, while the microfibrilar component remained. New formations of eulanin elastic fibres were observed three days post papain instillation. After ten days the interalveolar oedema had disappeared and the elastic fibres were of normal morphology although irregular groups of strips of elastic fibres were evident. A mixed pattern of panlobular, centrilobular and normal lung zones were observed. Two months after papain instillation abundant accumulations of elastic fibres of irregular outline were observed associated to collagen fibres. In conclusion, the morphometric parameters studied showed a significant progression of the emphysema. The strong correlation between NF and MLI suggested that papain-induced emphysema is principally caused by breaches of the alveolar walls. The results seem to point to a very abnormal remodelling process associated with elastic fibre regeneration, although there were no signs of destruction of these new fibres formed in emphysematous rat lung induced by papain.
authors.affiliation: Department of Cell Biology, Medical School, Aging Institute, University of Murcia, Murcia, Spain. bioetica@um.es
authors.forename: L M
authors.initials: LM
authors.lastname: Pastor
authors.forename: F
authors.initials: F
authors.lastname: Sánchez-Gascón
authors.forename: J C
authors.initials: JC
authors.lastname: Girona
authors.forename: C M
authors.initials: CM
authors.lastname: Bernal-Mañas
authors.forename: E
authors.initials: E
authors.lastname: Morales
authors.forename: E
authors.initials: E
authors.lastname: Beltrán-Frutos
authors.forename: M
authors.initials: M
authors.lastname: Canteras
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004547:Elastic Tissue / Q000473:pathology* / Q000648:ultrastructure; D009024:Morphogenesis / Q000187:drug effects*; D010206:Papain / Q000009:adverse effects*; D011654:Pulmonary Edema; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D014132:Trachea
chemical_list: D010206:Papain