Buprenorphine decreases CCL2-mediated migration of CD14+CD16+ monocytes

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...

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Bibliographic Details
Published in:Journal of leukocyte biology 2018-05, Vol.104 (6), p.1049-1059
Main Authors: Jaureguiberry-Bravo, Matias, Lopez, Lillie, Berman, Joan W.
Format: Article
Language:English
Online Access:Get full text
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Summary: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 MOR and full antagonist of KOR. 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.
ISSN:0741-5400
1938-3673
DOI:10.1002/JLB.3HI0118-015R