title: Differential synthesis and release of IL-18 and IL-18 Binding Protein from human platelets and their implications for HIV infection.
abstract: IL-18 is a pro-inflammatory cytokine belonging to the IL-1 family and is produced in the body from macrophages, epithelial and dendritic cells, keratinocytes, adrenal cortex etc. The cytokine is produced as an inactive precursor that is cleaved inside cells into its mature form by activated caspase 1, which exists as an inactive precursor in human cells and requires assembly of an inflammasomes for its activation. We show here for the first time that human platelets contain transcripts for the IL-18 gene. They synthesize the cytokine de novo, process and release it upon activation. The activation also results in the assembly of an inflammasome and activation of caspase-1. Platelets also contain the IL-18 antagonist, the IL-18-Binding Protein (IL-18BP); however, it is not synthesized in them de novo, is present in pre-made form and is released irrespective of platelet activation. IL-18 and IL-18BP co-localize to α granules inside platelets and are secreted out with different kinetics. Platelet activation contributes to plasma concentrations in healthy individuals, as their plasma samples contain abundant IL-18, while their platelet-poor plasma samples contain very little amounts of the cytokine. The plasma and PPP samples from these donors, however, contain comparable amounts of IL-18BP. Unlike healthy individuals, the platelet-poor plasma from HIV-infected individuals contains significant amounts of IL-18. Our findings have important implications for viral infections and other human diseases that are accompanied by platelet activation.
authors.affiliation: Laboratory of Innate Immunity, CHU Ste-Justine Research Center/Department of Microbiology, Infectiology & Immunology, University of Montreal, Montreal, QC, Canada.
authors.forename: Ossama
authors.initials: O
authors.lastname: Allam
authors.affiliation: Laboratory of Innate Immunity, CHU Ste-Justine Research Center/Department of Microbiology, Infectiology & Immunology, University of Montreal, Montreal, QC, Canada.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Samarani
authors.affiliation: Department of Biological Sciences, University of Quebec at Montreal (UQAM), Montreal, Quebec, Canada.
authors.forename: Mohammad-Ali
authors.initials: MA
authors.lastname: Jenabian
authors.affiliation: Division of Hematology & Chronic Viral Illness Service, McGill University, Montreal, QC, Canada.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
authors.affiliation: CHUM/Department of Microbiology, Infectiology & Immunology, University of Montreal, Montreal, QC, Canada.
authors.forename: Cecile
authors.initials: C
authors.lastname: Tremblay
authors.affiliation: CHU Ste-Justine Research Center/Department of Pediatrics, University of Montreal, Montreal, QC, Canada.
authors.forename: Devendra
authors.initials: D
authors.lastname: Amre
authors.affiliation: Laboratory of Innate Immunity, CHU Ste-Justine Research Center/Department of Microbiology, Infectiology & Immunology, University of Montreal, Montreal, QC, Canada. Electronic address: ali.ahmad@recherche-ste-justine.qc.ca.
authors.forename: Ali
authors.initials: A
authors.lastname: Ahmad
mesh_terms: D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000378:metabolism* / Q000473:pathology; D015497:HIV-1; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D020382:Interleukin-18 / Q000096:biosynthesis*; D020014:K562 Cells; D008297:Male; D022142:Secretory Vesicles / Q000378:metabolism / Q000473:pathology
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; C118370:interleukin-18 binding protein
keywords: IL-18; IL-18BP; Platelet activation; Platelets; Thrombin