| Progranulin is a chemoattractant for microglia and stimulates their endocytic activity. | |
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MedLine Citation:
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PMID: 21224065 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mutations resulting in progranulin haploinsufficiency cause disease in patients with a subset of frontotemporal lobar degeneration; however, the biological functions of progranulin in the brain remain unknown. To address this subject, the present study initially assessed changes in gene expression and cytokine secretion in rat primary cortical neurons treated with progranulin. Molecular pathways enriched in the progranulin gene set included cell adhesion and cell motility pathways and pathways involved in growth and development. Secretion of cytokines and several chemokines linked to chemoattraction but not inflammation were also increased from progranulin-treated primary neurons. Therefore, whether progranulin is involved in recruitment of immune cells in the brain was investigated. Localized lentiviral expression of progranulin in C57BL/6 mice resulted in an increase of Iba1-positive microglia around the injection site. Moreover, progranulin alone was sufficient to promote migration of primary mouse microglia in vitro. Primary microglia and C4B8 cells demonstrated more endocytosis of amyloid β1-42 when treated with progranulin. These data demonstrate that progranulin acts as a chemoattractant in the brain to recruit or activate microglia and can increase endocytosis of extracellular peptides such as amyloid β. |
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Authors:
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Fiona Pickford; Jacob Marcus; Luiz Miguel Camargo; Qiurong Xiao; Danielle Graham; Jan-Rung Mo; Matthew Burkhardt; Vinayak Kulkarni; Jamie Crispino; Heike Hering; Michael Hutton |
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Publication Detail:
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Type: Journal Article Date: 2010-12-23 |
Journal Detail:
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Title: The American journal of pathology Volume: 178 ISSN: 1525-2191 ISO Abbreviation: Am. J. Pathol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-12 Completed Date: 2011-04-18 Revised Date: 2012-01-02 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 284-95 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Neuroscience Drug Discovery, Merck Research Laboratories, Boston, Massachusetts 02115, USA. fiona_pickford@merck.com |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Brain / drug effects, metabolism, physiology* Calcium-Binding Proteins / metabolism Cell Line, Tumor Cell Movement Chemotactic Factors / genetics, pharmacology, physiology* Cytokines / metabolism Endocytosis* / drug effects Humans Intercellular Signaling Peptides and Proteins / genetics, pharmacology, physiology* Mice Mice, Mutant Strains Microfilament Proteins Microglia / drug effects, metabolism, physiology* Neurons / drug effects, metabolism, physiology Rats |
| Chemical | |
Reg. No./Substance:
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0/Aif1 protein, mouse; 0/Calcium-Binding Proteins; 0/Chemotactic Factors; 0/Cytokines; 0/GRN protein, human; 0/Intercellular Signaling Peptides and Proteins; 0/Microfilament Proteins |
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