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Evaluation of the effects of inhibition of the Rho/Rho-kinase in the eosinophils adhesion in patients with sickle cell anemia and in asthma experimental model in sickle mice

Grant number: 11/02380-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): July 01, 2011
Effective date (End): February 28, 2015
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Carla Fernanda Franco Penteado
Grantee:Flávia Rubia Pallis
Home Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:08/57441-0 - Clinical, cellular and molecular alterations in hemoglobinopathies and other hereditary hemolytic anemias, AP.TEM

Abstract

Sickle cell disease (SCD) is caused by a single base substitution in codon 6 (GAG/GTC ) of the beta globin gene, leading to production of hemoglobin S. The fundamental event in the pathogenesis of sickle cell anemia (SCA ) is the polymerization of HbS . Currently it is widely accepted that leukocytes also play an important role in the pathophysiology of the disease, adhering to the endothelium and participating in oxidative stress and inflammation. Neutrophils appear to be the most leukocytes that participate in the process of vaso -occlusion, although it is also possible the participation of eosinophils in this phenomenon. Eosinophils are intensely involved in inflammatory processes mainly airway. Data from our laboratory have shown that eosinophils of patients with AF have adhesive properties, enhanced chemotaxis and degranulation capacity. However, the involvement of eosinophils in the pathophysiology of AF is still not well established. Besides leukocytes, the endothelium also plays a key role in the spread and perpetuation of the chronic inflammatory process that characterizes the AF. Therefore this project aims to evaluate the adhesion of eosinophils to the endothelium of patients with AF under inflammatory conditions. Furthermore, we evaluate the role of Rho GTPases , proteins that regulate intracellular signaling pathways involved in the organization of the cytoskeleton , adhesion and proliferation, eosinophil adhesion to endothelium. Thus , with this study we intend to have a better understanding of the role of eosinophils and Rho GTPases in vaso- occlusion in AF process , and these data may help to clarify the different clinical manifestations , especially pulmonary complications of the disease .