Genetic deficiency of alpha(1)-PI in mice influences lung responses to bleomycin

It has recently been suggested that proteinase inhibitors modulate the fibr otic response in the lung. This study investigated the development of bleom ycin-induced pulmonary changes in pallid mice, deficient in serum al-protei nase inhibitor, and with a lower elastase inhibitory capacity, and in conge nic 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 o f biochemical, morphological and morphometrical methods. In both strains, 21 and 72 h after bleomycin, the lungs showed foci of infl ammatory cell infiltration associated with emphysema. Fibrosis developed,vi th time after bleomycin. At 14 days fibrosis affected 23.46 +/- 9.48% (mean +/- SD) and 40.62 +/- 13.33% (p < 0.01) of the lungs of C57Bl/6J and palli d 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 mic e bleomycin increased lung hydroxyproline content by 34% and desmosine cont ent by 44% (p <0.01 for both). In pallid mice these increases mere only 21% (p <0.01) and 6%, which may reflect parenchymal loss. Thus, the lung destructive response (emphysema) and the subsequent prolifer ative reaction (fibrosis) to bleomycin are potentiated in alpha (1)-protein ase inhibitor deficiency.