Monocyte chemotactic protein-1 regulates voltage-gated K+ channels and macrophage transmigration

Howard E. Gendelman, Shengyuan Ding, Nan Gong, Jianuo Liu, Servio H. Ramirez, Yuri Persidsky, R. Lee Mosley, Tong Wang, David J. Volsky, Huangui Xiong

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Progressive human immunodeficiency virus (HIV)-1 infection and virus-induced neuroinflammatory responses effectuate monocyte-macrophage transmigration across the blood-brain barrier (BBB). A key factor in mediating these events is monocyte chemotactic protein-1 (MCP-1). Upregulated glial-derived MCP-1 in HIV-1-infected brain tissues generates a gradient for monocyte recruitment into the nervous system. We posit that the inter-relationships between MCP-1, voltage-gated ion channels, cell shape and volume, and cell mobility underlie monocyte transmigration across the BBB. In this regard, MCP-1 serves both as a chemoattractant and an inducer of monocyte-macrophage ion flux affecting cell shape and mobility. To address this hypothesis, MCP-1-treated bone marrow-derived macrophages (BMM) were analyzed for gene and protein expression, electrophysiology, and capacity to migrate across a laboratory constructed BBB. MCP-1 enhanced K+ channel gene (KCNA3) and channel protein expression. Electrophysiological studies revealed that MCP-1 increased outward K+ currents in a dose-dependent manner. In vitro studies demonstrated that MCP-1 increased BMM migration across an artificial BBB, and the MCP-1-induced BMM migration was blocked by tetraethylammonium, a voltage-gated K+ channel blocker. Together these data demonstrated that MCP-1 affects macrophage migratory movement through regulation of voltage-gated K+ channels and, as such, provides a novel therapeutic strategy for neuroAIDS.

Original languageEnglish (US)
Pages (from-to)47-59
Number of pages13
JournalJournal of Neuroimmune Pharmacology
Volume4
Issue number1
DOIs
StatePublished - Mar 2009

Keywords

  • Blood-brain barrier
  • K channels
  • Monocyte
  • Monocyte chemotactic protein-1

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

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