In vivo evaluation of the role of eosinophil in the vaso-occlusion process using sickle cell transgenic mice: Involvement of Rho-quinase pathway

Abstract

In sickle cell anemia (SCA), leukocyte plays an important role in the pathophysiology of disease, and leukocyte adhesion may in fact be the initiating event in vaso-occlusive episodes. The neutrophil appears to be the leukocyte that most participates in the vaso-occlusive process, at least in sickle mice, although mononuclear cells and eosinophils probably also contribute. Preliminary results demonstrated that eosinophils from SCA patients exist in an activated state (Pallis et al, 2013). In addition, recent results indicated that RhoA/ROCK pathway play an important role in the eosinophil adhesion to the endothelium and, the inhibition of this signaling pathway could alleviates asthma in SCA. Under flow conditions, the number of eosinophils adhered to HUVEC cells was reduced when they were treated with RhoA/ROCK inhibitors. In vivo OVA induced lung inflammation was significantly reduced by pretreatment with the RhoA/ROCK pathway in sickle cell mice. However, the role of eosinophil in the vaso-oclusive process in not well establish. Thus, the aim of this study was to determine the role of eosinophils in vaso-occlusion process in sickle cell anemia, using intravital microscopy techniques. Moreover, we will also evaluated the effect of inhibitors of the RhoA/ROCK pathway in the eosinophil adhesion and migration in sickle cell mice. (AU)