Chemokine induction of both glial and peripheral elements: Implications for HIV encephalitis

C. M. McManus, K. Weidenheim, J. W. Berman

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

We are studying the role of chemokines and their receptors in the pathogenesis of HIV encephalitis, a major CNS complication of AIDS. Chemokines and their receptors maintain opposing roles in HIV infection; certain C-C chemokines compete with virus for binding to their receptors, a protective mechanism, where as chemokine receptors play a permissive role in HIV infection by functioning as coreceptors for entry of the virus into the cell. This study analyzes in vitro regulation of chemokines and their receptors in response to chemokines in major cells of HIV encephalitis: human microglia, astrocytes, and peripheral blood monocytes. Chemokine treatment of any of these cells with MIP-1α, MIP-1β, or MCP-1 results in induction of these chemokines in a dose and time dependent manner as measured by RNase protection assay(RPA) and ELISA. C-C chemokine receptors were also analyzed by RPA demonstrating that astrocytes have no detectable levels of these receptors despite their ability to respond to chemokines suggesting that there are as yet unidentified receptor(s). Both microglia and PBMs constitutively express several C-C receptors and respond to chemokines by regulating their receptor expression. Brain sections of AIDS cases, encephalitogenic, nonencephalitogenic, and aged matched normals were analyzed by immunohistochemistry for expression of chemokines. MIP-1α, MIP-1β, and MCP-1 are expressed by glial elements as well as monocytic cells in encephalitogenic brains. There was minimal staining of all chemokines in nonencephalitogenic brains and controls. An understanding of how chemokines and their receptors are regulated in the CNS is critical for determining treatment strategies for HIV encephalitis.

Original languageEnglish (US)
Pages (from-to)A647
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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