title: Characterization of platelet-monocyte complexes in HIV-1-infected individuals: possible role in HIV-associated neuroinflammation.
abstract: HIV-1-associated neuroinflammation persists even with effective combined antiretroviral therapy, and it is associated with the presence of activated monocytes/macrophages within the CNS. To infiltrate the CNS, monocytes transmigrate across the selectively permeable blood-brain barrier, which is compromised during HIV-1 infection. Interestingly, platelet-derived excess soluble CD40 ligand found in the plasma and cerebrospinal fluid of HIV-1-infected individuals with cognitive impairment has previously been implicated in increased blood-brain barrier permeability. In this study we show that soluble CD40 ligand also promotes the formation of complexes between inflammatory monocytes and activated platelets (PMCs), which are detected by flow cytometry as monocytes that express excess of CD61, a platelet marker, and that these complexes are increased in individuals with HIV-1 infection. PMCs exhibit an enhanced ability to adhere to human brain microvascular endothelial cells as compared with monocytes alone, and they migrate across the transendothelial barrier. These complexes can be found marginalized in the lumen of postcapillary venules in postmortem brain tissue derived from cases of HIV-1-associated encephalitis. The extravasation of monocytes across the brain endothelium may exacerbate neuroinflammation, indicating that enhancing this event via platelet interaction may be a contributing factor in the development of cognitive impairment. Thus, dampening platelet activation, and in turn PMC formation, with antiplatelet agents may prove beneficial in developing adjunctive therapies for use in combination with combined antiretroviral therapy in an effort to reduce HIV-1-associated neurologic deficit.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642.
authors.forename: Meera V
authors.initials: MV
authors.lastname: Singh
authors.forename: Donna C
authors.initials: DC
authors.lastname: Davidson
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Jackson
authors.forename: Vir B
authors.initials: VB
authors.lastname: Singh
authors.forename: Jharon
authors.initials: J
authors.lastname: Silva
authors.forename: Servio H
authors.initials: SH
authors.lastname: Ramirez
authors.forename: Sanjay B
authors.initials: SB
authors.lastname: Maggirwar
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000276:immunology* / Q000473:pathology; D001812:Blood-Brain Barrier / Q000276:immunology* / Q000473:pathology; D023201:CD40 Ligand / Q000276:immunology; D002560:Cerebrovascular Circulation / Q000276:immunology; D004660:Encephalitis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D042783:Endothelial Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D039661:Integrin beta3 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000473:pathology
chemical_list: C061248:ITGB3 protein, human; D039661:Integrin beta3; D023201:CD40 Ligand
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