Genetic deficiency of alpha1-PI in mice influences lung responses to bleomycin.
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.
Cavarra
E
E
Dept of Physiopathology and Experimental Medicine, University of Siena, Italy.
Martorana
P A
PA
Bartalesi
B
B
Fineschi
S
S
Gambelli
F
F
Lucattelli
M
M
Ortiz
L
L
Lungarella
G
G
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*
D000900:Anti-Bacterial Agents; D000515:alpha 1-Antitrypsin; D001761:Bleomycin