Expression of the secondary granule proteins major basic protein 1 (MBP-1) and eosinophil peroxidase (EPX) is required for eosinophilopoiesis in mice

• Published in: Blood Vol. 122; no. 5; pp. 781 - 790
• Main Authors: Doyle, Alfred D., Jacobsen, Elizabeth A., Ochkur, Sergei I., McGarry, Michael P., Shim, Kevin G., Nguyen, David T.C., Protheroe, Cheryl, Colbert, Dana, Kloeber, Jake, Neely, Joseph, Shim, Kelly P., Dyer, Kimberly D., Rosenberg, Helene F., Lee, James J., Lee, Nancy A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2013; American Society of Hematology
• Subjects: Animals; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Bone Marrow Cells - physiology; Cell Differentiation - drug effects; Cell Differentiation - genetics; Cell Proliferation - drug effects; Cells, Cultured; Eosinophil Major Basic Protein - genetics; Eosinophil Major Basic Protein - metabolism; Eosinophil Major Basic Protein - physiology; Eosinophil Peroxidase - genetics; Eosinophil Peroxidase - metabolism; Eosinophil Peroxidase - physiology; Eosinophils - drug effects; Eosinophils - metabolism; Eosinophils - physiology; Interleukin-5 - pharmacology; Leukocyte Count; Mice; Mice, Inbred C57BL; Mice, Knockout; Myelopoiesis - drug effects; Myelopoiesis - genetics; Myelopoiesis - physiology; Phagocytes, Granulocytes, and Myelopoiesis
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2013-01-473405

Eosinophil activities are often linked with allergic diseases such as asthma and the pathologies accompanying helminth infection. These activities have been hypothesized to be mediated, in part, by the release of cationic proteins stored in the secondary granules of these granulocytes. The majority of the proteins stored in these secondary granules (by mass) are major basic protein 1 (MBP-1) and eosinophil peroxidase (EPX). Unpredictably, a knockout approach targeting the genes encoding these proteins demonstrated that, unlike in mice containing a single deficiency of only MBP-1 or EPX, the absence of both granule proteins resulted in the near complete loss of peripheral blood eosinophils with no apparent impact on any other hematopoietic lineage. Moreover, the absence of MBP-1 and EPX promoted a concomitant loss of eosinophil lineage-committed progenitors in the marrow, identifying a specific blockade in eosinophilopoiesis as the causative event. Significantly, this blockade of eosinophilopoiesis is also observed in ex vivo cultures of marrow progenitors and is not rescued in vivo by adoptive bone marrow engraftment, suggesting a cell-autonomous defect in marrow progenitors. These observations implicate a role for granule protein gene expression as a regulator of eosinophilopoiesis and provide another strain of mice congenitally deficient of eosinophils. •The loss of the two most abundant eosinophil granule proteins disrupts the production of blood eosinophils from marrow progenitors.•Knockout animals deficient for both MBP-1 and EPX represent a novel strain of mice with a specific and congenital loss of eosinophils.