Lung Pathologies in a Chronic Inflammation Mouse Model Are Independent of Eosinophil Degranulation.
| Title: | Lung Pathologies in a Chronic Inflammation Mouse Model Are Independent of Eosinophil Degranulation. |
|---|---|
| Authors: | Jacobsen EA; 1 Division of Pulmonary Medicine and.; Ochkur SI; 1 Division of Pulmonary Medicine and.; Doyle AD; 1 Division of Pulmonary Medicine and.; LeSuer WE; 1 Division of Pulmonary Medicine and.; Li W; 2 Department of Medicine, Guizhou Provincial People's Hospital, Guizhou, China; and.; Protheroe CA; 3 Division of Hematology/Oncology, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, Arizona.; Colbert D; 3 Division of Hematology/Oncology, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, Arizona.; Zellner KR; 1 Division of Pulmonary Medicine and.; Shen HH; 2 Department of Medicine, Guizhou Provincial People's Hospital, Guizhou, China; and.; Irvin CG; 4 Vermont Lung Center, Department of Medicine, University of Vermont, Burlington, Vermont.; Lee JJ; 1 Division of Pulmonary Medicine and.; Lee NA; 3 Division of Hematology/Oncology, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, Arizona. |
| Source: | American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 2017 May 15; Vol. 195 (10), pp. 1321-1332. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: American Thoracic Society Country of Publication: United States NLM ID: 9421642 Publication Model: Print Cited Medium: Internet ISSN: 1535-4970 (Electronic) Linking ISSN: 1073449X NLM ISO Abbreviation: Am J Respir Crit Care Med Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2000- : New York, NY : American Thoracic Society; Original Publication: New York, NY : American Lung Association, c1994- |
| MeSH Terms: | Eosinophils/*metabolism ; Inflammation/*metabolism ; Inflammation/*pathology ; Lung/*metabolism ; Lung/*pathology; Chemokine CCL24/metabolism ; Interleukin-5/metabolism ; Th2 Cells/metabolism ; Animals ; Chronic Disease ; Disease Models, Animal ; Flow Cytometry ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic |
| Abstract: | Rationale: The release of eosinophil granule proteins in the lungs of patients with asthma has been dogmatically linked with lung remodeling and airway hyperresponsiveness. However, the demonstrated inability of established mouse models to display the eosinophil degranulation occurring in human subjects has prevented a definitive in vivo test of this hypothesis.; Objectives: To demonstrate in vivo causative links between induced pulmonary histopathologies/lung dysfunction and eosinophil degranulation.; Methods: A transgenic mouse model of chronic T-helper cell type 2-driven inflammation overexpressing IL-5 from T cells and human eotaxin 2 in the lung (I5/hE2) was used to test the hypothesis that chronic histopathologies and the development of airway hyperresponsiveness occur as a consequence of extensive eosinophil degranulation in the lung parenchyma.; Measurement and Main Results: Studies targeting specific inflammatory pathways in I5/hE2 mice surprisingly showed that eosinophil-dependent immunoregulative events and not the release of individual secondary granule proteins are the central contributors to T-helper cell type 2-induced pulmonary remodeling and lung dysfunction. Specifically, our studies highlighted a significant role for eosinophil-dependent IL-13 expression. In contrast, extensive degranulation leading to the release of major basic protein-1 or eosinophil peroxidase was not causatively linked to many of the induced pulmonary histopathologies. However, these studies did define a previously unappreciated link between the release of eosinophil peroxidase (but not major basic protein-1) and observed levels of induced airway mucin.; Conclusions: These data suggest that improvements observed in patients with asthma responding to therapeutic strategies ablating eosinophils may occur as a consequence of targeting immunoregulatory mechanisms and not by simply eliminating the destructive activities of these purportedly end-stage effector cells. |
| Comments: | Comment in: Am J Respir Crit Care Med. 2017 May 15;195(10):1281-1282. doi: 10.1164/rccm.201612-2435ED.. (PMID: 28504602) |
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| Contributed Indexing: | Keywords: asthma; chronic inflammation; eosinophil peroxidase; lung; major basic protein |
| Substance Nomenclature: | 0 (Chemokine CCL24); 0 (Interleukin-5) |
| Entry Date(s): | Date Created: 20161207 Date Completed: 20170719 Latest Revision: 20181113 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC5443899 |
| DOI: | 10.1164/rccm.201606-1129OC |
| PMID: | 27922744 |
| Database: | MEDLINE |
Journal Article