5
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Intracerebral GM-CSF contributes to transendothelial monocyte migration in APP/PS1 Alzheimer’s disease mice

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Although tight junctions between human brain microvascular endothelial cells in the blood–brain barrier prevent molecules or cells in the bloodstream from entering the brain, in Alzheimer’s disease, peripheral blood monocytes can “open” these tight junctions and trigger subsequent transendothelial migration. However, the mechanism underlying this migration is unclear. Here, we found that the CSF2RB, but not CSF2RA, subunit of the granulocyte-macrophage colony-stimulating factor receptor was overexpressed on monocytes from Alzheimer’s disease patients. CSF2RB contributes to granulocyte-macrophage colony-stimulating factor-induced transendothelial monocyte migration. Granulocyte-macrophage colony-stimulating factor triggers human brain microvascular endothelial cells monolayer tight junction disassembly by downregulating ZO-1 expression via transcription modulation and claudin-5 expression via the ubiquitination pathway. Interestingly, intracerebral granulocyte-macrophage colony-stimulating factor blockade abolished the increased monocyte infiltration in the brains of APP/PS1 Alzheimer’s disease model mice. Our results suggest that in Alzheimer’s disease patients, high granulocyte-macrophage colony-stimulating factor levels in the brain parenchyma and cerebrospinal fluid induced blood–brain barrier opening, facilitating the infiltration of CSF2RB-expressing peripheral monocytes across blood–brain barrier and into the brain. CSF2RB might be useful as an Alzheimer’s disease biomarker. Thus, our findings will help to understand the mechanism of monocyte infiltration in Alzheimer’s disease pathogenesis.

          Related collections

          Author and article information

          Journal
          J Cereb Blood Flow Metab
          J. Cereb. Blood Flow Metab
          JCB
          spjcb
          Journal of Cerebral Blood Flow & Metabolism
          SAGE Publications (Sage UK: London, England )
          0271-678X
          1559-7016
          21 July 2016
          November 2016
          : 36
          : 11
          : 1978-1991
          Affiliations
          [1-0271678X16660983]Department of Developmental Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, P.R. China
          Author notes
          [*]Yu H Chen, Department of Developmental Cell Biology, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province 110122, China. Email: yhchen@ 123456mail.cmu.edu.cn
          Article
          PMC5094311 PMC5094311 5094311 10.1177_0271678X16660983
          10.1177/0271678X16660983
          5094311
          27444968
          29916ba1-dd61-4d54-a57c-80f67b62c283
          © The Author(s) 2016
          History
          : 1 March 2016
          : 31 May 2016
          : 27 June 2016
          Categories
          Original Articles

          Alzheimer’s disease,CSF2RB,granulocyte-macrophage colony-stimulating factor,monocyte infiltration

          Comments

          Comment on this article