THE INVOLVEMENT OF MATRIX MIETALLOPROTEINASES IN BASEMENT MEMBRANE INJURY IN ACUTE ALLERGIC AIRWAY INFLAMMATION
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概要
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Airway remodeling in bronchial asthma such as subepithelial fibrosis is thought to be one of the repair processes that follows the continuing injury as of chronic airway inflammation. However, the injury mechanisms of epithelial basement membrane (BM) remain unclear. Airway inflammation in asthma is characterized with the infiltration of inflammatory cells such as eosinophils and lymphocytes to the airways. Previously, we demonstrated a critical role of matrix metalloproteinase (MMP)-2 and -9 in the cellular infiltration using a murine model of allergic asthma (J. Immunol., 162: 4212, 1999). These MMPs have a potential to cleave collagen IV which is one of the major constituents of BM. Therefore, we hypothesized that the accumulation of inflammatory cells to airways cause BM injury through the degradation of matrix components by MMPs. To evaluate our hypothesis, we investigated the ultrastructural changes of BM and the immunoreactivity of collagen III and IV, using our murine model. The disruption of the lamina densa and matrix construction and the decrease of the immunoreactivity for type IV collagen in subepithelium were observed in association with the accumulation of inflammatory cells and the increased MMP activities in airways 3 days after allergen inhalation. This disorganization of the matrix components in the subepithelium, as well the cellular accumulation, was abolished by the administration of TIMIP-2 and dexamethasone. The immunoreactivity for type IV collagen in the subepithelium in allergen-inhaled mice returned to the level of that in saline-inhaled mice 10 days after inhalation in association with the decrease of the cell numbers and MMP activities in airways. The immunoreactivity for type III collagen was changed neither 3 nor 10 days after allergen inhalation. These results suggest that epithelial basement membrane gets injured by, at least in part, MMPs as a consequence of cell transmigration through the membrane during acute allergic airway inflammation.
- 日本結合組織学会の論文
著者
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SENOO Haruki
Department of Cell Biology and Histology, Akita University School of Medicine
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Imai Katsuyuki
Department of Anatomy, Akita University School of Medicine
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Nawata Jun
Cardiovascular Medicine Tohoku University Graduate School Of Medicine
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OHNO Isao
Department of Pathophysiology, Tohoku Pharmaceutical University
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Senoo Haruki
Department Of Anatomy Akita University School Of Medicine
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Shirato Kunio.
Cardiovascular Medicine Tohoku University Graduate School Of Medicine
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Hattori Toshio
Department Of Infectious And Respiratory Diseases Tohoku University Graduate School Of Medicine
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Imai Katsuyuki
Department Of Anatomy Akita University School Of Medicine
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OKADA Shinji
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The U
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Ohno I
Department Of Pathophysiology Tohoku Pharmaceutical University
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Ohno Isao
Department Of Infectious And Respiratory Diseases Tohoku University Graduate School Of Medicine
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Ohno Isao
Department Of Electronics Faculty Of Engineering Tamagawa University
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Okada Shinji
Department Of Infectious And Respiratory Diseases Tohoku University Graduate School Of Medicine
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Okada Shinji
Department Of Applied Biological Chemistry Graduate School Of Agricultural And Life Sciences The Uni
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Kumagai Katsunori
Cardiovascular Medicine, Tohoku University Graduate School of Medicine
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Hayashi Katutoshi
Cardiovascular Medicine, Tohoku University Graduate School of Medicine
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Kumagai Katsunori
Cardiovascular Medicine Tohoku University Graduate School Of Medicine
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Hayashi Katutoshi
Cardiovascular Medicine Tohoku University Graduate School Of Medicine
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