Evolution of endotoxin-induced lung injury in the rat beyond the acute phase.
OBJECTIVE
Intratracheal endotoxin in rats causes acute lung injury. Here we have addressed the cellular physiopathology of lung recovery from that injury.


METHODS
The lungs of 5 untreated rats and rats treated with intratracheal endotoxin from 2, 3, 5, 8 (5 rats each) and 15 days (2 rats) were studied by light and electron microscopy and immunohistochemistry.


RESULTS
In the acute phase there was a reduction in the aerated spaces (p < 0.01); diffuse infiltration of granulocytes and macrophages; hyperplasia of type-II pneumocytes, and hypertrophy of interstitial cells. Aerated spaces improved during recovery. In the early recovery phase (3-8 days) the compartmentalization of infiltrating cells varied significantly (p < 0.01): macrophages remained widespread while neutrophils were inside blood vessels. Many pneumocytes were intermediate between type-I and type-II cells. In the late recovery phase (15 days) the infiltrate disappeared; myofibroblasts were significantly more than previously (p < 0.01) and extracellular matrix was abundant; type-II pneumocytes contained non-lamellated lipid inclusions.


CONCLUSIONS
Macrophages play a pivotal role in the damage-repair processes of the lung following endotoxin injury, leading to an increase in extracellular matrix, differentiation of myofibroblasts and altered secretion of surfactant by newly differentiated type-II pneumocytes.
Domenici
L
L
Department of Anatomy, Histology and Forensic Medicine, University of Florence, Florence, Italy. l.domenici@unifi.it
Pieri
L
L
Gallè
M B
MB
Romagnoli
P
P
Adembri
C
C
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity*; D004847:Epithelial Cells / Q000473:pathology; D005109:Extracellular Matrix / Q000473:pathology; D005347:Fibroblasts / Q000473:pathology; D006098:Granulocytes / Q000276:immunology; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects* / Q000473:pathology* / Q000648:ultrastructure; D008854:Microscopy, Electron; D011663:Pulmonary Surfactants / Q000378:metabolism; D051381:Rats; D012128:Respiratory Distress Syndrome / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*
D004731:Endotoxins; D011663:Pulmonary Surfactants