Suppressive effect of anti-alpha 1-antichymotrypsin serum on pulmonary fibrosis induced by phorbol myristate acetate in vivo.
BACKGROUND
PMA induces pulmonary fibrosis in the rabbit (1). Pulmonary fibrosis induced by PMA occurs in the alveolar wall and has the same pattern as idiopathic pulmonary fibrosis (IPF)(2), so this system can be used as an animal model for IPF. PMA also increases the content of alpha-1-antichymotrypsin (ACT) in cultured alveolar macrophages of bronchoalveolar lavages (BAL), and dexamethasone inhibits this PMA-induced increase (3). Here we investigated the role of ACT in pulmonary fibrosis induced by PMA.


METHODS
Rabbits were treated intratracheally for 6 days with saline, dimethyl sulphoxide (DMSO) used as a solvent of PMA, PMA dissolved in DMSO or PMA plus anti-ACT rabbit serum. BAL samples were obtained. ACT in cell pellet and cell-free fluid of BAL were assayed by radioimmunoassay. Sections of the lung were examined histologically by a point count method. The ratio of fibrosis to elastosis (fibrotic ratio) was evaluated for each rabbit by the ratio of total points of collagen stained by the Azan-Mallory method to those of elastic fiber stained by the Elastica van Gieson method. Hydroxyproline (HP) was assayed biochemically, and the amount of HP in the alveolar wall for each rabbit was calculated using the assayed values of HP and the ratio of histologic collagen points in the alveolar wall to those in the lung tissue by a point count method.


RESULTS
The fibrotic ratio of the PMA group increased fourfold compared with that of the saline group. The ratio of the PMA plus anti-ACT group decreased and was similar to that of the saline group. The ratio of the DMSO group was about two times as much as that of the saline or the PMA plus anti-ACT groups. The calculated amount of hydroxyproline in the alveolar wall of the PMA group increased and was approximately 1.5-fold compared with that of the saline group. The amount of HP of the PMA plus anti-ACT group decreased and was similar to that of the saline group. In the BAL, the amount and the percentage of ACT in cell pellet per macrophage of the PMA group increased more than those of the saline and DMSO groups. The amount and percentage of the PMA plus anti-ACT group were significantly less than those of the PMA group. Those of the DMSO group were similar to those of the saline group.


CONCLUSIONS
These findings suggest that anti-ACT has a suppressive effect on pulmonary fibrosis induced by PMA and that ACT is important in the PMA model of pulmonary fibrosis.
D000818:Animals; D001798:Blood Proteins / Q000276:immunology* / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002478:Cells, Cultured; D003094:Collagen / Q000032:analysis / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004195:Disease Models, Animal; D006909:Hydroxyproline / Q000032:analysis / Q000378:metabolism; D008168:Lung / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D016676:Macrophages, Alveolar / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D011817:Rabbits; D011863:Radioimmunoassay; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*; D000514:alpha 1-Antichymotrypsin / Q000032:analysis / Q000276:immunology* / Q000502:physiology
D001798:Blood Proteins; D000514:alpha 1-Antichymotrypsin; D003094:Collagen; D013755:Tetradecanoylphorbol Acetate; D006909:Hydroxyproline; D004121:Dimethyl Sulfoxide