Genetic deficiency of α₁‐PI in mice influences lung responses to bleomycin (original) (raw)

It has recently been suggested that proteinase inhibitors modulate the fibrotic response in the lung. This study investigated the development of bleomycininduced pulmonary changes in pallid mice, deficient in serum a 1-proteinase inhibitor, and with a lower elastase inhibitory capacity, and in congenic C57Bl/6J mice. Male pallid and C57Bl/6J mice received a single intratracheal instillation of either saline or bleomycin. The investigation was carried out by means of biochemical, morphological and morphometrical methods. In both strains, 21 and 72 h after bleomycin, the lungs showed foci of inflammatory cell infiltration associated with emphysema. Fibrosis developed with time after bleomycin. At 14 days fibrosis affected 23.46¡9.48% (mean¡SD) and 40.62¡13.34% (pv0.01) of the lungs of C57Bl/6J and pallid mice, respectively. Emphysema affected 3.68¡3.11% and 12.57¡4.13% (pv0.01) of lung in C57Bl/6J and pallid mice, respectively. In C57Bl/6J mice bleomycin increased lung hydroxyproline content by 34% and desmosine content by 44% (pv0.01 for both). In pallid mice these increases were only 21% (pv0.01) and 6%, which may reflect parenchymal loss. Thus, the lung destructive response (emphysema) and the subsequent proliferative reaction (fibrosis) to bleomycin are potentiated in a 1-proteinase inhibitor deficiency.