title: Hydroxycarbamide reduces eosinophil adhesion and degranulation in sickle cell anaemia patients.
abstract: Inflammation, leucocyte and red cell adhesion to the endothelium contribute to the pathogenesis of sickle cell anaemia. Neutrophils appear to be important for vaso-occlusion, however, eosinophils may also participate in this phenomenon. The role of eosinophils in the pathophysiology of sickle cell anaemia (SCA) and the effect of hydroxycarbamide (HC) therapy on the functional properties of these cells are not understood. Patients with SCA and those on HC therapy (SCAHC) were included in the study. SCAHC individuals presented significantly lower absolute numbers of eosinophils than SCA. Furthermore, SCAHC eosinophils demonstrated significantly lower adhesive properties, compared to SCA eosinophils. SCA and SCAHC eosinophils presented greater spontaneous migration when compared with control eosinophils. Baseline eosinophil peroxidase and reactive oxygen species release was higher for SCA individuals than for control individuals, as were plasma levels of eosinophil derived neurotoxin. SCAHC eosinophil degranulation was lower than that of SCA eosinophil degranulation. Eotaxin-1 and RANTES levels were higher in the plasma of SCA and SCAHC individuals, when compared with controls. These data suggest that eosinophils exist in an activated state in SCA and indicate that these cells play a role in the vaso-occlusive process. The exact mechanism by which HC may alter SCA eosinophil properties is not clear.
authors.affiliation: Haematology and Haemotherapy Centre - Instituto Nacional de Ciência e Tecnologia do Sangue (INCTS), UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Flavia Rubia
authors.initials: FR
authors.lastname: Pallis
authors.forename: Nicola
authors.initials: N
authors.lastname: Conran
authors.forename: Kleber Yotsumoto
authors.initials: KY
authors.lastname: Fertrin
authors.forename: Sara Terezinha
authors.initials: ST
authors.lastname: Olalla Saad
authors.forename: Fernando Ferreira
authors.initials: FF
authors.lastname: Costa
authors.forename: Carla Fernanda
authors.initials: CF
authors.lastname: Franco-Penteado
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000755:Anemia, Sickle Cell / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D000986:Antisickling Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects*; D002462:Cell Membrane / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology* / Q000627:therapeutic use; D039041:Integrin alpha4beta1 / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000378:metabolism; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D000986:Antisickling Agents; C504120:CEACAM8 protein, human; D015815:Cell Adhesion Molecules; D016207:Cytokines; D058851:GPI-Linked Proteins; D039041:Integrin alpha4beta1; D016177:Macrophage-1 Antigen; D017382:Reactive Oxygen Species; D006918:Hydroxyurea
keywords: chemokines; eosinophils; inflammation; sickle cell anaemia