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Progranulin is located in secretory granules and vesicles of neutrophils and macrophages by immunogold electron microscopy
Author(s) -
Lin WenLang,
Zehr Cynthia,
Lewis Jada,
Dickson Dennis W.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a22-b
Subject(s) - immunogold labelling , pathology , biology , microbiology and biotechnology , proinflammatory cytokine , chemistry , inflammation , ultrastructure , medicine , immunology
Progranulin is a mediator of development, tumorigenesis and wound repair. Mutations in the gene for progranulin cause frontotemporal dementia. Little is known about the role of progranulin in the nervous system. The cleavage products of progranulin, granulins, were first isolated from granule‐enriched fractions of human and equine neutrophils and from rat bone marrow. Immunohistochemistry of granulin has been reported in macrophages or monocytes. Here we use a post‐embedding immunogold labeling method to ultrastructurally localize progranulin in mouse and human tissue. Bone marrow from mouse femoral bone was fixed in 4% paraformaldehyde. Human choroid plexus and a brain abscess were obtained from autopsy brains fixed in formalin. Tissues were dehydrated in ethanols, infiltrated and embedded in LR White resin. Thin sections were collected on Formvar‐coated nickel grids and incubated with antibodies to mouse or human progranulin, followed by gold‐conjugated secondary antibodies. In all tissues progranulin was localized to secretory granules and vesicles in neutrophils and macrophages. Labeled granules had morphological features of secretory granules. They were membrane‐bound vesicles with pale to optically dense contents and ranged from 200 to 500 microns in diameter. This is the first report of the ultrastructural localization of progranulin to mouse and human neutrophils and macrophages in normal and inflammatory conditions, including neuroinflammatory disorders.