title: Genetic deficiency of alpha1-PI in mice influences lung responses to bleomycin.
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 alpha1-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 alpha1-proteinase inhibitor deficiency.
authors.affiliation: Dept of Physiopathology and Experimental Medicine, University of Siena, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Cavarra
authors.forename: P A
authors.initials: PA
authors.lastname: Martorana
authors.forename: B
authors.initials: B
authors.lastname: Bartalesi
authors.forename: S
authors.initials: S
authors.lastname: Fineschi
authors.forename: F
authors.initials: F
authors.lastname: Gambelli
authors.forename: M
authors.initials: M
authors.lastname: Lucattelli
authors.forename: L
authors.initials: L
authors.lastname: Ortiz
authors.forename: G
authors.initials: G
authors.lastname: Lungarella
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D001761:Bleomycin / Q000009:adverse effects*; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000515:alpha 1-Antitrypsin / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D000515:alpha 1-Antitrypsin; D001761:Bleomycin