Frontline Science: Eosinophil-deficient MBP-1 and EPX double-knockout mice link pulmonary remodeling and airway dysfunction with type 2 inflammation.
| Title: | Frontline Science: Eosinophil-deficient MBP-1 and EPX double-knockout mice link pulmonary remodeling and airway dysfunction with type 2 inflammation. |
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| Authors: | Ochkur SI; Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, Arizona, USA.; Division of Hematology/Oncology, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, Arizona, USA.; Doyle AD; Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, Arizona, USA.; Jacobsen EA; Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, Arizona, USA.; LeSuer WE; Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, Arizona, USA.; Division of Hematology/Oncology, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, Arizona, USA.; Li W; Department of Medicine, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China; and.; Protheroe CA; Division of Hematology/Oncology, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, Arizona, USA.; Zellner KR; Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, Arizona, USA.; Colbert D; Division of Hematology/Oncology, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, Arizona, USA.; Shen HH; Department of Medicine, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China; and.; Irvin CG; Vermont Lung Center, Department of Medicine, University of Vermont, Burlington, Vermont, USA.; Lee JJ; Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, Arizona, USA.; Lee NA; Division of Hematology/Oncology, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, Arizona, USA; nlee@mayo.edu. |
| Source: | Journal of leukocyte biology [J Leukoc Biol] 2017 Sep; Vol. 102 (3), pp. 589-599. Date of Electronic Publication: 2017 May 17. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural |
| Language: | English |
| Journal Info: | Publisher: Oxford University Press Country of Publication: England NLM ID: 8405628 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1938-3673 (Electronic) Linking ISSN: 07415400 NLM ISO Abbreviation: J Leukoc Biol Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2023- : Oxford : Oxford University Press; Original Publication: New York : Alan R. Liss, c1984- |
| MeSH Terms: | Airway Remodeling/*immunology ; Asthma/*immunology ; Eosinophil Major Basic Protein/*deficiency ; Eosinophil Peroxidase/*deficiency ; Eosinophils/*immunology ; Lung/*immunology; Asthma/genetics ; Asthma/pathology ; Eosinophil Major Basic Protein/immunology ; Eosinophil Peroxidase/immunology ; Eosinophils/pathology ; Lung/pathology ; Animals ; Mice ; Mice, Knockout |
| Abstract: | Eosinophils and the release of cationic granule proteins have long been implicated in the development of the type 2-induced pathologies linked with respiratory inflammation. Paradoxically, the ablation of the two genes encoding the most abundant of these granule proteins, major basic protein-1 (MBP-1) and eosinophil peroxidase (EPX), results in a near collapse of eosinophilopoiesis. The specificity of this lineage ablation and the magnitude of the induced eosinopenia provide a unique opportunity to clarify the importance of eosinophils in acute and chronic inflammatory settings, as well as to identify potential mechanism(s) of action linked with pulmonary eosinophils in those settings. Specifically, we examined these issues by assessing the induced immune responses and pathologies occurring in MBP-1-/-/EPX-/- mice after 1) ovalbumin sensitization/provocation in an acute allergen-challenge protocol, and 2) crossing MBP-1-/-/EPX-/- mice with a double-transgenic model of chronic type 2 inflammation (i.e., I5/hE2). Acute allergen challenge and constitutive cytokine/chemokine expression each induced the accumulation of pulmonary eosinophils in wild-type controls that was abolished in the absence of MBP-1 and EPX (i.e., MBP-1-/-/EPX-/- mice). The expression of MBP-1 and EPX was also required for induced lung expression of IL-4/IL-13 in each setting and, in turn, the induced pulmonary remodeling events and lung dysfunction. In summary, MBP-1-/-/EPX-/- mice provide yet another definitive example of the immunoregulatory role of pulmonary eosinophils. These results highlight the utility of this unique strain of eosinophil-deficient mice as part of in vivo model studies investigating the roles of eosinophils in health and disease settings.; (© Society for Leukocyte Biology.) |
| Comments: | Comment in: J Leukoc Biol. 2017 Sep;102(3):571-573. doi: 10.1189/jlb.3CE0317-127R.. (PMID: 28860205) |
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| Grant Information: | R01 HL065228 United States HL NHLBI NIH HHS |
| Contributed Indexing: | Keywords: asthma; chronic inflammation; eosinophil peroxidase; lung; major basic protein |
| Substance Nomenclature: | EC 1.11.1.- (Eosinophil Peroxidase); EC 3.1.27.- (Eosinophil Major Basic Protein) |
| Entry Date(s): | Date Created: 20170519 Date Completed: 20171006 Latest Revision: 20220408 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC5557640 |
| DOI: | 10.1189/jlb.3HI1116-488RR |
| PMID: | 28515227 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural