Bleomycin-induced pulmonary fibrosis in genetically mast cell-deficient WBB6F1-W/Wv mice and mechanism of the suppressive effect of tranilast, an antiallergic drug inhibiting mediator release from mast cells, on fibrosis.
It has been well known that the number of mast cells increases during the development of fibrosis in various tissues including the lung. However, the role of mast cells in fibrosis still remains obscure. In the present paper, we evidenced that pulmonary fibrosis could be induced in genetically mast cell-deficient WBB6F1-W/Wv mice as well as WBB6F1-(+/+) mice having mast cells normally by the treatment with bleomycin (BLM, 5 mg/kg, i.v., 10 days), and there was not much difference in the histological changes of lungs between the two strains. An increase in the hydroxyproline content of the lung of WBB6F1-W/Wv mice was rather higher than that of WBB6F1-(+/+) mice. Previously, we reported that tranilast, an antiallergic drug inhibiting chemical mediator release from mast cells, suppressed the development of BLM-induced pulmonary fibrosis in ICR mice, suggesting the possibility that mast cells play certain roles in fibrosis. However, it was evidenced in the present report that tranilast suppressed BLM-induced fibrosis in WBB6F1-W/Wv mice. Tranilast neither suppressed the cytotoxic activity of BLM against KB cells and L-929 cells in vitro, nor inhibited the antitumor activity of BLM against Sarcoma-180 transplanted subcutaneously into ICR mice. Tranilast may act through suppressing BLM-induced activation of lymphoid cells including macrophage and neutrophil. These results indicate an inconsequential role of mast cells in the development of fibrosis. Increases in the number of mast cells and in histamine content of the lung, which were widely reported in the lungs of BLM-treated mice, may be the result of fibrosis.
Mori
H
H
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Kawada
K
K
Zhang
P
P
Uesugi
Y
Y
Sakamoto
O
O
Koda
A
A
D000704:Analysis of Variance; D000818:Animals; D001761:Bleomycin; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D006909:Hydroxyproline / Q000096:biosynthesis; D008168:Lung / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology*; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D062367:ortho-Aminobenzoates; D001761:Bleomycin; C012293:tranilast; D006909:Hydroxyproline