title: Involvement of interstitial cells in endotoxin-induced acute lung injury. A histochemical and electron microscopical study.
abstract: Instillation of endotoxin into the rat trachea causes a disease representative of the lung response to several types of inflammatory injury and--in part--of human acute respiratory distress syndrome. Oxidizing radicals, including nitric oxide (NO), may be suspected to play some role in these conditions. The participation of leukocytes to tissue damage in these conditions has been reported, but the behaviour of lung interstitial cells in unknown. In this study, we have investigated on possible sources of NO and the response of lung interstitial cells during endotoxin-induced experimental lung injury. Rats were subjected to intratracheal instillation of endotoxin (5 mg/kg body weight) and sacrificed after 12, 24 and 48 h; animals treated with saline or sham-operated were used as controls. Analyses included conventional light microscopy, histochemical detection of NADPH-diaphorase (which co-localizes with NO synthase) and electron microscopy. Lung infiltrates appeared after 12 h and became progressively more severe up to 48 h. NADPH-diaphorase positive cells appeared in the septa after 24 h and became more numerous after 48 h; their nuclei were smooth-surfaced and the cytoplasm often extended into projections. By electron microscopy, only interstitial fibroblasts had a morphology similar to that of NO synthase positive cells and increased in number in the septa at the same time. These cells formed incomplete cuffs around blood capillaries and became large and rich in endoplasmic reticulum, as compared to those of the controls. These data suggest that hypertrophic fibroblastic interstitial cells can concur to maintain capillaries dilated (by NO secretion) and impair respiratory gas diffusion (by intervening between capillaries and pneumocytes), during experimental acute respiratory distress in the rat.
authors.affiliation: Department of Human Anatomy and Histology and Institute of Anesthesiology and Intensive Care, University of Florence, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Domenici
authors.forename: C
authors.initials: C
authors.lastname: Adembri
authors.forename: G P
authors.initials: GP
authors.lastname: Novelli
authors.forename: P
authors.initials: P
authors.lastname: Romagnoli
mesh_terms: D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D004731:Endotoxins / Q000494:pharmacology; D005347:Fibroblasts / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D015388:Organelles / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure*; D051381:Rats; D017208:Rats, Wistar; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology
chemical_list: D004731:Endotoxins; D009569:Nitric Oxide; D009252:NADPH Dehydrogenase