Abstract
It has recently been suggested that proteinase inhibitors modulate the fibrotic response in the lung. This study investigated the development of bleomycin-induced pulmonary changes in pallid mice, deficient in serum α1‐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% (p<0.01) of the lungs of C57Bl/6J and pallid mice, respectively. Emphysema affected 3.68±3.11% and 12.57±4.13% (p<0.01) 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% (p<0.01 for both). In pallid mice these increases were only 21% (p<0.01) and 6%, which may reflect parenchymal loss.
Thus, the lung destructive response (emphysema) and the subsequent proliferative reaction (fibrosis) to bleomycin are potentiated in α1‐proteinase inhibitor deficiency.
This work was supported by a grant from Ministero dell'Universita' e della Ricerca Scientifica e Tecnologica.
- Received February 2, 2000.
- Accepted September 25, 2000.
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