Avaliação funcional dos eosinófilos na anemia falciforme e o efeito do tratamento com hidroxiureia / Altered functional properties of eosinophils in sickle cell anemia and effects of hydroxyurea therapy

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

13/05/2011

RESUMO

Sickle cell anemia is the homozygous state for hemoglobin S. Inflammation plays an important role in the vaso-occlusive process of the disease, where leukocytes, proinflammatory cytokines and adhesion molecules are increased in the peripheral blood of patients with sickle cell anemia. Leukocytosis is associated with morbidity and mortality in these patients. Moreover, neutrophils from sickle cell patients show increased chemotactic and adhesive properties. However, there is little evidence about the possible functional changes in eosinophils and production of mediators derived from these cells. The eosinophils are involved in airway inflammatory processes and are numerically larger and have increased adhesive properties in sickle cell anemia. The lungs are particularly vulnerable to vaso-occlusive events in sickle cell anemia and pulmonary complications are the leading causes of death and second most common cause of hospitalization in these patients. Hydroxyurea is currently the only drug used to treat the clinical manifestations of sickle cell anemia by increasing the levels of fetal hemoglobin, reducing the hemoglobin S polymerization, neutrophils and some complications associated with vaso-occlusive phenomenon. Considering the scarcity of studies that have evaluated the role of eosinophils in the pathophysiology of sickle cell anemia, this project aimed to compare the adhesive properties, chemotaxis capacity, degranulation and production of mediators in eosinophils of patients with sickle cell anemia. Furthermore, we investigated whether treatment with hydroxyurea interferes with the function of eosinophils. Blood samples from patients with sickle cell anemia were analyzed and showed higher absolute number of eosinophils compared with patients without treatment with hydroxyurea and control subjects. The basal adhesion of eosinophils from patients treated with hydroxyurea confirmed that these cells are more adhesive to fibronectin than eosinophils of patients with sickle cell disease without the same treatment and control subjects. Moreover, there was no change in the adhesion of these cells when stimulated with chemokines (RANTES, Eotaxin, IL-5). Flow cytometry was used to compare the expression and activation of major adhesion molecules in these eosinophils, and we identified an increased expression of ? subunit of integrin Mac-1 in patients with sickle cell disease without treatment with hydroxyurea. Eosinophils from patients with sickle cell disease, treated or not with hydroxyurea, had a higher capacity for spontaneous migration and chemotaxis in response to chemotactic agents (RANTES, Eotaxin, IL-5). Moreover, these patients had higher serum and plasma RANTES and Eotaxin-1. Eosinophils from patients with sickle cell anemia had increased degranulation and a consequently higher amount of released eosinophil peroxidase and eosinophil-derived neurotoxin than patients who were treated with hydroxyurea and control subjects, but the co-incubation with RANTES, Eotaxin and IL-5 did not alter this response. Finally, there was an increased production of reactive oxygen species in these patients. Overall, our results suggest that eosinophils contribute significantly to the process of vasoocclusion observed in sickle cell anemia.

ASSUNTO(S)

eosinofilos anemia falciforme inflamação quimiocinas eosinophils sickle cell anemia inflammation chemokines

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