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Alterations in the lung distribution of hyaluronan and versican in a murine model of asthma
S188 Abstracts
J ALLERGY CLIN IMMUNOL FEBRUARY 2004
651
Alterations in the Lung Distribution of Hyaluronan and Versican in a Murine Model of Asthma
MONDAY
T. S. Wilkinson1, E. Chi2, W. Henderson, Jr.2, S. Lara3, S. Potter-Perigo1, M. Merrilees4, L. Altman1, T. Wight1; 1Vascular Biology, Hope Heart Institute, Seattle, WA, 2Department of Medicine, University of Washington, Seattle, WA, 3Department of Pathology, University of Washington, Seattle, WA, 4Department of Anatomy and Radiology, University of Auckland, Auckland, NEW ZEALAND. RATIONALE: Hyaluronan (HA) and versican are important extracellular matrix components of the lung in health and disease. Dramatic increases in HA and versican have been demonstrated, in animal models of fibrosis and inflammation, in both lung tissue and bronchoalveolar lavage fluid. In addition, HA and versican have been shown to increase smooth muscle cell proliferation and leukocyte adhesion. Collectively these findings suggest that HA and versican may promote inflammation and remodeling in asthma and other chronic lung diseases. METHODS: We used the well-characterized model of ovalbumininduced asthma to study the distribution of HA, versican and other ECM components within the inflamed murine lung. RESULTS: HA and versican were markedly increased in ovalbumin treated mice compared to controls and were co-localized around the smooth muscle cells of the bronchi and their associated arteries. Connective tissue septa of ovalbumin treated mice had significant increases in HA expression around smaller veins and this was often localized to vessels where leukocyte margination could be seen. Ovalbumin treatment also induced a prominent border of HA and versican along the visceral pleura and the alveolar walls and capillaries, which was minimal or absent in control mice. There were no dramatic differences in collagen, elastin, total glycosaminoglycans or smooth muscle cell architecture between experimental and control mice. CONCLUSIONS: Our data suggest that changes in HA and versican induced by allergic inflammation might precede remodeling events, such as collagen deposition, and so contribute to disease progression. Targeting HA and versican may be an attractive therapeutic modality for treating inflammatory diseases of the lung. Funding: GlaxoSmithKline
J ALLERGY CLIN IMMUNOL FEBRUARY 2004
651
Alterations in the Lung Distribution of Hyaluronan and Versican in a Murine Model of Asthma
MONDAY
T. S. Wilkinson1, E. Chi2, W. Henderson, Jr.2, S. Lara3, S. Potter-Perigo1, M. Merrilees4, L. Altman1, T. Wight1; 1Vascular Biology, Hope Heart Institute, Seattle, WA, 2Department of Medicine, University of Washington, Seattle, WA, 3Department of Pathology, University of Washington, Seattle, WA, 4Department of Anatomy and Radiology, University of Auckland, Auckland, NEW ZEALAND. RATIONALE: Hyaluronan (HA) and versican are important extracellular matrix components of the lung in health and disease. Dramatic increases in HA and versican have been demonstrated, in animal models of fibrosis and inflammation, in both lung tissue and bronchoalveolar lavage fluid. In addition, HA and versican have been shown to increase smooth muscle cell proliferation and leukocyte adhesion. Collectively these findings suggest that HA and versican may promote inflammation and remodeling in asthma and other chronic lung diseases. METHODS: We used the well-characterized model of ovalbumininduced asthma to study the distribution of HA, versican and other ECM components within the inflamed murine lung. RESULTS: HA and versican were markedly increased in ovalbumin treated mice compared to controls and were co-localized around the smooth muscle cells of the bronchi and their associated arteries. Connective tissue septa of ovalbumin treated mice had significant increases in HA expression around smaller veins and this was often localized to vessels where leukocyte margination could be seen. Ovalbumin treatment also induced a prominent border of HA and versican along the visceral pleura and the alveolar walls and capillaries, which was minimal or absent in control mice. There were no dramatic differences in collagen, elastin, total glycosaminoglycans or smooth muscle cell architecture between experimental and control mice. CONCLUSIONS: Our data suggest that changes in HA and versican induced by allergic inflammation might precede remodeling events, such as collagen deposition, and so contribute to disease progression. Targeting HA and versican may be an attractive therapeutic modality for treating inflammatory diseases of the lung. Funding: GlaxoSmithKline