Emphysema requires the receptor for advanced glycation end-products triggering on structural cells

Koichi Waseda, Nobuaki Miyahara, Akihiko Taniguchi, Etsuko Kurimoto, Genyo Ikeda, Hikari Koga, Utako Fujii, Yasuhiko Yamamoto, Erwin W. Gelfand, Hiroshi Yamamoto, Mitsune Tanimoto, Arihiko Kanehiro

Research output: Contribution to journalArticle

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Abstract

Pulmonary emphysema is characterized by persistent inflammation and progressive alveolar destruction. The receptor for advanced glycation end-products (RAGE) is a multiligand cell surface receptor reported to be involved in the process of acute alveolar epithelial cell injury.However, studies that address the role ofRAGE in pulmonary emphysema are inconclusive. We investigated the role of RAGE in the development of elastase-induced pulmonary inflammation and emphysema in mice. RAGE-sufficient (RAGE1/1) mice and RAGE-deficient (RAGE2/2) mice were treatedwith intratracheal elastase on Day 0. Airway inflammation, static lung compliance, lung histology, and the levels of neutrophil-related chemokine and proinflammatory cytokines in bronchoalveolar lavage fluid were determined on Days 4 and 21. Neutrophilia in bronchoalveolar lavage fluid, seen in elastase-treated RAGE1/1 mice, was reduced in elastase-treated RAGE2/2 mice on Day 4, and was associated with decreased levels of keratinocyte chemoattractant, macrophage inflammatory protein-2, and IL-1b. Static lung compliance values and emphysematous changes in the lung tissue were decreased in RAGE2/2 mice compared with RAGE1/1 mice on Day 21 after elastase treatment. Experiments using irradiated, bone marrow-chimeric mice showed that themice expressingRAGEon radioresistant structural cells, but not hematopoietic cells, developed elastase-induced neutrophilia and emphysematous change in the lung. In contrast, mice expressing RAGE on hematopoietic cells, but not radioresistant structural cells, showed reduced neutrophilia and emphysematous change in the lung. These data identify the importance of RAGE expressed on lung structural cells in the development of elastase-induced pulmonary inflammation and emphysema. Thus, RAGE represents a novel therapeutic target for preventing pulmonary emphysema.

Original languageEnglish
Pages (from-to)482-491
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume52
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

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Pancreatic Elastase
Emphysema
Pulmonary Emphysema
Lung
Lung Compliance
Bronchoalveolar Lavage Fluid
Pneumonia
Chemokine CXCL2
Inflammation
Alveolar Epithelial Cells
Histology
Fluids
Chemotactic Factors
Cell Surface Receptors
Advanced Glycosylation End Product-Specific Receptor
Keratinocytes
Chemokines
Bone
Neutrophils
Bone Marrow

Keywords

  • Elastase
  • Emphysema
  • Receptor for advanced glycation end-products

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Emphysema requires the receptor for advanced glycation end-products triggering on structural cells. / Waseda, Koichi; Miyahara, Nobuaki; Taniguchi, Akihiko; Kurimoto, Etsuko; Ikeda, Genyo; Koga, Hikari; Fujii, Utako; Yamamoto, Yasuhiko; Gelfand, Erwin W.; Yamamoto, Hiroshi; Tanimoto, Mitsune; Kanehiro, Arihiko.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 52, No. 4, 01.04.2015, p. 482-491.

Research output: Contribution to journalArticle

Waseda, K, Miyahara, N, Taniguchi, A, Kurimoto, E, Ikeda, G, Koga, H, Fujii, U, Yamamoto, Y, Gelfand, EW, Yamamoto, H, Tanimoto, M & Kanehiro, A 2015, 'Emphysema requires the receptor for advanced glycation end-products triggering on structural cells', American Journal of Respiratory Cell and Molecular Biology, vol. 52, no. 4, pp. 482-491. https://doi.org/10.1165/rcmb.2014-0027OC
Waseda, Koichi ; Miyahara, Nobuaki ; Taniguchi, Akihiko ; Kurimoto, Etsuko ; Ikeda, Genyo ; Koga, Hikari ; Fujii, Utako ; Yamamoto, Yasuhiko ; Gelfand, Erwin W. ; Yamamoto, Hiroshi ; Tanimoto, Mitsune ; Kanehiro, Arihiko. / Emphysema requires the receptor for advanced glycation end-products triggering on structural cells. In: American Journal of Respiratory Cell and Molecular Biology. 2015 ; Vol. 52, No. 4. pp. 482-491.
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