Tohoku J. Exp. Med., 2004, 203(4)

Chymase is Activated in the Pulmonary Inflammation and Fibrosis Induced by Paraquat in Hamsters

KENSUKE ORITO, YUKO SUZUKI, HIROSHI MATSUDA,¹ MITSUYUKI SHIRAI and FUMIAKI AKAHORI

Department of Veterinary Pharmacology, School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa 229-8501, and
¹Laboratory of Clinical Immunology, Department of Veterinary Medicine Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183-8509

The involvement of chymase has been implicated in fibrotic response to tissue injuries. Besides its direct action, chymase indirectly promotes fibrotic response by generating angiotensin (Ang) II from Ang I. In the present study, we examined whether chymase and angiotensin converting enzyme (ACE), that also generates Ang II, were activated in the pulmonary inflammation and fibrosis induced by paraquat (PQ) in hamsters. In an acute PQ intoxication group, PQ was administered subcutaneously and the lungs were excised four days after administration. In a chronic PQ intoxication group, PQ was administered at the same dose once a week for six weeks. The lungs were excised five weeks after the last administration. On dissection, alveolar hemorrhage and capillary stasis were found in the acute PQ intoxication group while interstitial pulmonary fibrosis was found in the chronic PQ intoxication group. The pulmonary tissue chymase activity was elevated in both intoxication groups when compared with a respective age-matched, vehicle (saline)-administered group. Pulmonary tissue ACE activity, on the other hand, decreased in both intoxication groups. These data suggested that activated chymase may be involved in the establishment of PQ-induced pulmonary fibrosis in hamsters.

keywords —— paraquat; pulmonary fibrosis; ACE; chymase

© 2004 Tohoku University Medical Press

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Address for reprints: Kensuke Orito, D.V.M., Ph.D., Department of Veterinary Pharmacology, School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa 229-8501, Japan.