Hydroxyurea therapy of a murine model of sickle cell anemia inhibits the progression of pneumococcal disease by down-modulating E-selectin.
Blood
; 119(8): 1915-21, 2012 Feb 23.
Article
em En
| MEDLINE
| ID: mdl-22130804
ABSTRACT
Sickle cell anemia is characterized by chronic hemolysis coupled with extensive vascular inflammation. This inflammatory state also mechanistically promotes a high risk of lethal, invasive pneumococcal infection. Current treatments to reduce vaso-occlusive complications include chronic hydroxyurea therapy to induce fetal hemoglobin. Because hydroxyurea also reduces leukocytosis, an understanding of the impact of this treatment on pneumococcal pathogenesis is needed. Using a sickle cell mouse model of pneumococcal pneumonia and sepsis, administration of hydroxyurea was found to significantly improve survival. Hydroxyurea treatment decreased neutrophil extravasation into the infected lung coincident with significantly reduced levels of E-selectin in serum and on pulmonary epithelia. The protective effect of hydroxyurea was abrogated in mice deficient in E-selectin. The decrease in E-selectin levels was also evident in human sickle cell patients receiving hydroxyurea therapy. These data indicate that in addition to induction of fetal hemoglobin, hydroxyurea attenuates leukocyte-endothelial interactions in sickle cell anemia, resulting in protection against lethal pneumococcal sepsis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pneumonia Pneumocócica
/
Selectina E
/
Hidroxiureia
/
Anemia Falciforme
Limite:
Animals
/
Child
/
Female
/
Humans
Idioma:
En
Revista:
Blood
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos