Introduction: Acute Lung Injury (ALI) is a widespread damage to cells and structures of the alveolar capillary membrane that occurs within hours to days of a predisposing insult. A comprehensive understanding of the mechanisms of apoptosis in the initial injury and repair of lung epithelial and endothelial cells and other key cells involved in ALI is lacking. Further information is required regarding cytokine-signaling pathways, patterns of gene and protein expression. The present study attempts to correlate various parameters of lung damage and expression of certain proteins that regulate the cell cycle in an experimental model of ALI.
Material and methods: ΑLI was induced in five groups of mice via inhalation of paraquat. The animals of each group were sacrificed on days 1,2,3,4 and 6, respectively and their lungs were examined for the following parametres: focal thickening of alveolar membranes, capillary congestion, pulmonary oedema, intra-alveolar haemorrhage, interstitial neutrophil infiltration and intra-alveolar neutrophil infiltration scored from 0 to 3 according to the severity of the pathological changes. Specimens were also examined with immunoassay for the quantitative expression (percentile) of Ki-67, TUNEL staining (Todd-mediated dUTP nick end- labeling), p21, p16, p27, Cyclin B, Cyclin D1 and Cyclin E. A control group of animals that were not exposed to paraquat was also studied.
Results: All variables were significantly altered in all the study groups as compared with the control group suggesting the deleterious effect of the paraquat inhalation. Focal thickening of alveolar membranes and intraalveolar haemorrhage were the more significant pathological changes. Multiple comparisons showed significantly higher mean differences in TUNEL staining and in the expression of ki-67, cyclins and cyclin-dependent kinase inhibitors (CDKIs) particularly after 2-3 days from the paraquat inhalation.
Conclusion: These findings implicate that lung tissue damage is characterized by enhanced cellular proliferation and apoptosis both being regulated by complex interactions of cyclins and CDKIs.