title: Platelet Activation in Human Immunodeficiency Virus Type-1 Patients Is Not Altered with Cocaine Abuse.
abstract: Recent work has indicated that platelets, which are anucleate blood cells, significantly contribute to inflammatory disorders. Importantly, platelets also likely contribute to various inflammatory secondary disorders that are increasingly associated with Human Immunodeficiency Virus Type-1 (HIV) infection including neurological impairments and cardiovascular complications. Indeed, HIV infection is often associated with increased levels of platelet activators. Additionally, cocaine, a drug commonly abused by HIV-infected individuals, leads to increased platelet activation in humans. Considering that orchestrated signaling mechanisms are essential for platelet activation, and that nuclear factor-kappa B (NF-κB) inhibitors can alter platelet function, the role of NF-κB signaling in platelet activation during HIV infection warrants further investigation. Here we tested the hypothesis that inhibitory kappa B kinase complex (IKK) activation would be central for platelet activation induced by HIV and cocaine. Whole blood from HIV-positive and HIV-negative individuals, with or without cocaine abuse was used to assess platelet activation via flow cytometry whereas IKK activation was analyzed by performing immunoblotting and in vitro kinase assays. We demonstrate that increased platelet activation in HIV patients, as measured by CD62P expression, is not altered with reported cocaine use. Furthermore, cocaine and HIV do not activate platelets in whole blood when treated ex vivo. Finally, HIV-induced platelet activation does not involve the NF-κB signaling intermediate, IKKβ. Platelet activation in HIV patients is not altered with cocaine abuse. These results support the notion that non-IKK targeting approaches will be better suited for the treatment of HIV-associated inflammatory disorders.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America.
authors.forename: Michelle
authors.initials: M
authors.lastname: Kiebala
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America.
authors.forename: Meera V
authors.initials: MV
authors.lastname: Singh
authors.affiliation: Division of Infectious Diseases, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Piepenbrink
authors.affiliation: Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America.
authors.forename: Xing
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Division of Infectious Diseases, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America.
authors.forename: James J
authors.initials: JJ
authors.lastname: Kobie
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America.
authors.forename: Sanjay B
authors.initials: SB
authors.lastname: Maggirwar
mesh_terms: D000328:Adult; D000779:Anesthetics, Local / Q000009:adverse effects*; D000818:Animals; D016022:Case-Control Studies; D003042:Cocaine / Q000009:adverse effects*; D019970:Cocaine-Related Disorders / Q000097:blood / Q000150:complications / Q000473:pathology* / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000473:pathology* / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects*; D015398:Signal Transduction
chemical_list: D000779:Anesthetics, Local; D016328:NF-kappa B; D051550:I-kappa B Kinase; D003042:Cocaine