TY - JOUR T1 - Genetic deficiency of α<sub>1</sub>‐PI in mice influences lung responses to bleomycin JF - European Respiratory Journal JO - Eur Respir J SP - 474 LP - 480 DO - 10.1183/09031936.01.17304740 VL - 17 IS - 3 AU - E. Cavarra AU - P.A. Martorana AU - B. Bartalesi AU - S. Fineschi AU - F. Gambelli AU - M. Lucattelli AU - L. Ortiz AU - G. Lungarella Y1 - 2001/03/01 UR - http://erj.ersjournals.com/content/17/3/474.abstract N2 - 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&lt;0.01) of the lungs of C57Bl/6J and pallid mice, respectively. Emphysema affected 3.68±3.11% and 12.57±4.13% (p&lt;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&lt;0.01 for both). In pallid mice these increases were only 21% (p&lt;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. ER -