title: A novel inflammatory role for platelets in sickle cell disease.
abstract: The severe pain, ischemia and organ damage that characterizes sickle cell disease (SCD) is caused by vaso-occlusion, which is the blockage of blood vessels by heterotypic aggregates of sickled erythrocytes and other cells. Vaso-occlusion is also a vasculopathy involving endothelial cell dysfunction, leukocyte activation, platelet activation and chronic inflammation resulting in the multiple adhesive interactions between cellular elements. Since platelets mediate inflammation as well as thrombosis via release of pro- and anti-inflammatory molecules, we hypothesized that platelets may play an active inflammatory role in SCD by secreting increased amounts of cytokines. Since platelets have been shown to contain mRNA and actively produce proteins, we also hypothesized that SCD platelets may contain increased cytokine mRNA. In this cross-sectional study, we sought to compare both the quantity of cytokines secreted and the cytokine mRNA content, between SCD and control platelets. We measured the secretion of Th1, Th2, and Th17-related cytokines from platelets in a cohort of SCD patients. We simultaneously measured platelet mRNA levels of those cytokines. Platelets from SCD patients secreted increased quantities of IL-1β, sCD40L, and IL-6 compared to controls. Secretion was increased in patients with alloantibodies. Additionally, mRNA of those cytokines was increased in SCD platelets. Platelets from sickle cell patients secrete increased amounts of inflammatory cytokines, and contain increased cytokine mRNA. These findings suggest a novel immunological role for platelets in SCD vasculopathy, in addition to their thrombotic role, and strengthen the rationale for the use of anti-platelet therapy in SCD.
authors.affiliation: a Department of Pediatric Hematology/Oncology , Memorial Sloan Kettering Cancer Center , New York , NY , USA .
authors.forename: Jennifer
authors.initials: J
authors.lastname: Davila
authors.affiliation: b Department of Hematology/Oncology , Children's Hospital at Montefiore , Bronx , NY , USA .
authors.forename: Deepa
authors.initials: D
authors.lastname: Manwani
authors.affiliation: c Department of Pathology , Montefiore Medical Center , Bronx , NY , USA .
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Vasovic
authors.affiliation: d Laboratory of Platelet Biology , New York Blood Center , New York , NY , USA , and.
authors.forename: Mauro
authors.initials: M
authors.lastname: Avanzi
authors.affiliation: c Department of Pathology , Montefiore Medical Center , Bronx , NY , USA .
authors.forename: Joan
authors.initials: J
authors.lastname: Uehlinger
authors.affiliation: b Department of Hematology/Oncology , Children's Hospital at Montefiore , Bronx , NY , USA .
authors.forename: Karen
authors.initials: K
authors.lastname: Ireland
authors.affiliation: d Laboratory of Platelet Biology , New York Blood Center , New York , NY , USA , and.|e Division of Pediatric Hematology and Oncology , Weill Cornell Medical College , New York , NY , USA.
authors.forename: W Beau
authors.initials: WB
authors.lastname: Mitchell
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D015415:Biomarkers; D001792:Blood Platelets / Q000378:metabolism*; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015539:Platelet Activation; D012333:RNA, Messenger / Q000235:genetics; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger
keywords: Cytokines; inflammation; platelet activation; platelets; sickle cell disease