Affiliation:
1. Department of Microbiology and Immunology, the Graduate Center for Toxicology, and the Department of Internal Medicine, University of Kentucky, College of Medicine , Lexington, Kentucky
Abstract
Abstract
Eosinophils have been shown to increase in tissues during many fibrotic conditions and consequently have been suggested to contribute to the development of fibrosis. This study tested the hypothesis that eosinophils are essential in the development of lung fibrosis in mice in response to bleomycin (BLM). Anti-IL-5 antibody was administered intraperitoneally into mice 2 h prior to endotracheal BLM inoculation and thereafter, every other day. Lung eosinophilia was evaluated by measurement of eosinophil peroxidase activity and confirmed by eosinophil counts in histologic sections. Lung fibrosis was evaluated by hydroxyproline content and confirmed by collagen staining in histological sections. Results demonstrated that BLM induced pronounced lung eosinophilia, which was maximal 7 days after BLM treatment and remained elevated through day 14, in C57Bl/6 SCID mice and CBA/J mice. In contrast, eosinophilia was a minor component in the lungs of wildtype C57Bl/6 mice after BLM treatment, although lung fibrosis developed similarly in all three strains of mice. Treatment with anti-IL-5 completely abrogated eosinophilia but failed to block pulmonary fibrosis induced by BLM in all mouse strains, including C57Bl/6 SCID, wildtype C57Bl/6 mice, and CBA/J mice. Analysis of cytokine mRNA by RNase-protection assay in C57Bl/6 SCID mice indicated that BLM treatment caused enhanced expression of the cytokines, TNF-α, and IL-6 at days 3, 7, and 14 post-BLM inoculation, regardless of whether eosinophils were depleted by anti-IL-5. Finally, the importance of eosinophils in lung fibrosis was examined in IL-5 gene knockout mice (IL-5tm1Kopf). BLM treatment induced significant lung fibrosis in IL-5 knockout mice in the absence of eosinophilia. These findings indicate that eosinophils are not an absolute requirement for BLM-induced pulmonary fibrosis in the mouse.
Publisher
Oxford University Press (OUP)
Subject
Cell Biology,Immunology,Immunology and Allergy
Reference34 articles.
1. The pulmonary toxicity of antineoplastic agents;Ginsberg;Semin. Oncol.,1982
2. Unraveling pulmonary fibrosis: the bleomycin model;Bowden;Lab. Invest.,1984
3. Pulmonary fibrosis;Dunnill;Histopathology,1990
4. Differential cellular analysis of bronchoalveolar lavage fluid obtained at various stages during the development of bleomycin-induced pulmonary fibrosis in the rat. Am. Rev. Respir;Thrall;Dis.,1982
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