Expression of the secondary granule proteins major basic protein 1 (MBP-1) and eosinophil peroxidase (EPX) is required for eosinophilopoiesis in mice. 2013

Alfred D Doyle, and Elizabeth A Jacobsen, and Sergei I Ochkur, and Michael P McGarry, and Kevin G Shim, and David T C Nguyen, and Cheryl Protheroe, and Dana Colbert, and Jake Kloeber, and Joseph Neely, and Kelly P Shim, and Kimberly D Dyer, and Helene F Rosenberg, and James J Lee, and Nancy A Lee
Division of Pulmonary Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA. .

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.

UI MeSH Term Description Entries
D007958 Leukocyte Count The number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells. Blood Cell Count, White,Differential Leukocyte Count,Leukocyte Count, Differential,Leukocyte Number,White Blood Cell Count,Count, Differential Leukocyte,Count, Leukocyte,Counts, Differential Leukocyte,Counts, Leukocyte,Differential Leukocyte Counts,Leukocyte Counts,Leukocyte Counts, Differential,Leukocyte Numbers,Number, Leukocyte,Numbers, Leukocyte
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D001854 Bone Marrow Cells Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells. Bone Marrow Cell,Cell, Bone Marrow,Cells, Bone Marrow,Marrow Cell, Bone,Marrow Cells, Bone
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004804 Eosinophils Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. Eosinophil
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015848 Interleukin-5 A cytokine that promotes differentiation and activation of EOSINOPHILS. It also triggers activated B-LYMPHOCYTES to differentiate into IMMUNOGLOBULIN-secreting cells. B-Cell Growth Factor-II,Eosinophil Differentiation Factor,IL-5,T-Cell Replacing Factor,BCGF-II,Differentiation Factor, Eosinophil,IL5,T-Cell-Replacing Factor,B Cell Growth Factor II,Interleukin 5,Replacing Factor, T-Cell,T Cell Replacing Factor
D047093 Eosinophil Major Basic Protein One of several basic proteins released from EOSINOPHIL cytoplasmic granules. Eosinophil major basic protein is a 14-kDa cytotoxic peptide with a pI of 10.9. In addition to its direct cytotoxic effects, it stimulates the release of variety of INFLAMMATION MEDIATORS. Eosinophil Basic Protein,Major Basic Protein, Eosinophil,MBP Protein, Eosinophil,Basic Protein, Eosinophil,Eosinophil MBP Protein
D047209 Eosinophil Peroxidase A 66-kDa peroxidase found in EOSINOPHIL granules. Eosinophil peroxidase is a cationic protein with a pI of 10.8 and is comprised of a heavy chain subunit and a light chain subunit. It possesses cytotoxic activity towards BACTERIA and other organisms, which is attributed to its peroxidase activity. Peroxidase, Eosinophil

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