Frontline Science: Buprenorphine decreases CCL2-mediated migration of CD14+ CD16+ monocytes

J Leukoc Biol. 2018 Dec;104(6):1049-1059. doi: 10.1002/JLB.3HI0118-015R. Epub 2018 May 23.


HIV infection of the CNS causes neuroinflammation and damage that contributes to the development of HIV-associated neurocognitive disorders (HAND) in greater than 50% of HIV-infected individuals, despite antiretroviral therapy (ART). Opioid abuse is a major risk factor for HIV infection. It has been shown that opioids can contribute to increased HIV CNS pathogenesis, in part, by modulating the function of immune cells. HIV enters the CNS within two weeks after peripheral infection by transmigration of infected monocytes across the blood brain barrier (BBB). CD14+ CD16+ monocytes are a mature subpopulation that is increased in number in the peripheral blood of HIV-infected people. Mature monocytes can be productively infected with HIV, and they transmigrate preferentially across the BBB in response to CCL2, a chemokine elevated in the CNS and CSF of HIV-infected people even with ART. Buprenorphine, an opioid derivate, is an opioid replacement therapy for heroin addiction. It is a partial agonist of μ-opioid receptor and full antagonist of κ-opioid receptor. The effects of buprenorphine on CCL2-mediated CD14+ CD16+ monocytes transmigration across the BBB, a critical mechanism that promotes neuroinflammation and HAND, have not been characterized. We showed for the first time that buprenorphine decreases several steps of CCL2-mediated human mature monocyte transmigration. We propose that buprenorphine treatment in the context of HIV infection could serve a dual purpose, to treat opioid addiction and also to reduce neuroinflammation. Additionally, buprenorphine may be used as a treatment for HAND not only in the context of opioid abuse.

Keywords: FROUNT; adhesion; chemotaxis; human; neuroAIDS; opioids.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • AIDS Dementia Complex / immunology
  • AIDS Dementia Complex / prevention & control
  • Buprenorphine / pharmacology*
  • Buprenorphine / therapeutic use
  • Cell Adhesion / drug effects
  • Cells, Cultured
  • Chemokine CCL2 / physiology*
  • Chemotaxis, Leukocyte / drug effects
  • GPI-Linked Proteins / analysis
  • Humans
  • Inflammation / drug therapy
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lipopolysaccharide Receptors / analysis
  • Monocytes / cytology
  • Monocytes / drug effects*
  • Nuclear Pore Complex Proteins / metabolism
  • Opioid-Related Disorders / drug therapy
  • Receptors, IgG / analysis
  • Receptors, Opioid, kappa / antagonists & inhibitors
  • Receptors, Opioid, mu / agonists*
  • THP-1 Cells
  • Transendothelial and Transepithelial Migration / drug effects*
  • Vascular Cell Adhesion Molecule-1 / metabolism


  • CCL2 protein, human
  • Chemokine CCL2
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Lipopolysaccharide Receptors
  • NUP85 protein, human
  • Nuclear Pore Complex Proteins
  • Receptors, IgG
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Buprenorphine