Morphine and Galectin-1 Modulate HIV-1 Infection of Human Monocyte-Derived Macrophages

Abstract

Morphine is a widely abused, addictive drug that modulates immune function. Macrophages are a primary reservoir of HIV-1; therefore, they play a role in the development of this disease, as well as impact the overall course of disease progression. Galectin-1 is a member of a family of β-galactoside–binding lectins that are soluble adhesion molecules and that mediate direct cell–pathogen interactions during HIV-1 viral adhesion. Because the drug abuse epidemic and the HIV-1 epidemic are closely interrelated, we propose that increased expression of galectin-1 induced by morphine may modulate HIV-1 infection of human monocyte-derived macrophages (MDMs). In this article, we show that galectin-1 gene and protein expression are potentiated by incubation with morphine. Confirming previous studies, morphine alone or galectin-1 alone enhance HIV-1 infection of MDMs. Concomitant incubation with exogenous galectin-1 and morphine potentiated HIV-1 infection of MDMs. We used a nanotechnology approach that uses gold nanorod–galectin-1 small interfering RNA complexes (nanoplexes) to inhibit gene expression for galectin-1. We found that nanoplexes silenced gene expression for galectin-1, and they reversed the effects of morphine on galectin-1 expression. Furthermore, the effects of morphine on HIV-1 infection were reduced in the presence of the nanoplex.

Galectin-1 suppresses methamphetamine induced neuroinflammation in human brain microvascular endothelial cells: Neuroprotective role in maintaining blood brain barrier integrity

“…Previously, we have shown that addictive drugs such as opiates like morphine and Meth increased the expression of Galectin-1 in human monocytes-derived macrophages (MDM) and exogenous Galectin-1 and morphine potentiated HIV-1 infection of MDM (Reynolds JL, et al 2012 a ; Reynolds JL, et al 2012 b ). These studies demonstrated that Galectin-1 was an important mediator involved in immune-mediated responses observed in HIV-1 infected drug abusing subjects and that Galectin-1 could be included as a therapeutic target in combination therapy for HIV-1 infected drug abusers.…”

“…Further, we have shown that the Galectin expression levels may be modulated by viral infections and inflammatory agents such as drugs of abuse but whether they directly or indirectly alter BBB permeability is not known. (Reynolds JL, et al 2012 a ; Reynolds JL, et al 2012 b ). …”

Opioids and Opioid Maintenance Therapies: Their Impact on Monocyte-Mediated HIV Neuropathogenesis

“…These effects were mediated, in part, by increased surface CCR5, supporting the concept that morphine enhances HIV entry into macrophages by regulating the surface expression of its co-receptors [92]. Another proposed mechanism is the regulation of adhesion molecules that mediate pathogen-host interactions [90]. Galectin -1 is a soluble adhesion molecule secreted by many cell types including macrophages.…”

“…It has been shown that morphine enhances HIV infection of and replication in macrophages and other CNS resident cells (Fig. 1C) [88–90]. Many factors have been proposed to contribute to this process.…”

“…Galectin -1 is a soluble adhesion molecule secreted by many cell types including macrophages. Morphine treatment of macrophages increased the expression and secretion of galectin-1 [90], and treatment with both morphine and galectin-1 increased HIV infection of macrophages [90]. Morphine treatment has also been shown to down regulate anti-viral molecules in macrophages, including interferon alpha and beta [89], and anti-HIV miRNAs [93].…”