title: Expression of the secondary granule proteins major basic protein 1 (MBP-1) and eosinophil peroxidase (EPX) is required for eosinophilopoiesis in mice.
abstract: 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.
authors.affiliation: Division of Pulmonary Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA. .
authors.forename: Alfred D
authors.initials: AD
authors.lastname: Doyle
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Jacobsen
authors.forename: Sergei I
authors.initials: SI
authors.lastname: Ochkur
authors.forename: Michael P
authors.initials: MP
authors.lastname: McGarry
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Shim
authors.forename: David T C
authors.initials: DT
authors.lastname: Nguyen
authors.forename: Cheryl
authors.initials: C
authors.lastname: Protheroe
authors.forename: Dana
authors.initials: D
authors.lastname: Colbert
authors.forename: Jake
authors.initials: J
authors.lastname: Kloeber
authors.forename: Joseph
authors.initials: J
authors.lastname: Neely
authors.forename: Kelly P
authors.initials: KP
authors.lastname: Shim
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Dyer
authors.forename: Helene F
authors.initials: HF
authors.lastname: Rosenberg
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Lee
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D047093:Eosinophil Major Basic Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D047209:Eosinophil Peroxidase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015848:Interleukin-5 / Q000494:pharmacology; D007958:Leukocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D038042:Myelopoiesis / Q000187:drug effects / Q000235:genetics* / Q000502:physiology
chemical_list: D015848:Interleukin-5; D047209:Eosinophil Peroxidase; D047093:Eosinophil Major Basic Protein