Sickle cell anemia (SCA) is a genetically inherited hemolytic disorder characterized by chronic inflammation. Cytokine expression affects the pivotal pathways that contribute to disease pathogenesis, but the mechanism...Sickle cell anemia (SCA) is a genetically inherited hemolytic disorder characterized by chronic inflammation. Cytokine expression affects the pivotal pathways that contribute to disease pathogenesis, but the mechanisms involved are not well understood. SCA is associated with a proinflammatory state, and an enhanced inflammatory response occurs during vasoocclusive crisis. The immune system thus plays an important role in this inflammatory condition, with several cell types secreting pro-inflammatory cytokines that contribute to the occurrence of common cyclical events in SCA patients, such as hemolysis, vascular occlusion and inflammation. Studies of these cytokines and chemokines in SCA patients have clarified the mechanisms that underlie this disease and highlighted the need for a better understanding of cytokine participation in SCA pathophysiology.展开更多
Sickle cell disease (SCD) is a genetic disorder characterized by a chronic inflammatory process, and new biomarkers have been studied as promising molecules for understanding the inflammation in its pathophysiology. T...Sickle cell disease (SCD) is a genetic disorder characterized by a chronic inflammatory process, and new biomarkers have been studied as promising molecules for understanding the inflammation in its pathophysiology. The hemolysis and the release of molecules associated to the hemoglobin (Hb) catabolism, such as free Hb, iron, and heme, generating a oxidant environment with production of reactive oxygen and nitrogen species. The immune system plays a very important role in the inflammation, with cells secreting pro-inflammatory cytokines and chemokines. There is also a nitric oxide (NO) resistance state, with an impaired NO bioactivity, leading to a vascular dys-function;activation of platelet, leukocytes, erythrocytes, and endothelial cells, with expression of adhesion molecules and its ligands, and several receptors, that altogether participate at inflammatory process. During inflammation, there is an increase of dendritic cells (DCs) expresse toll like receptors (TLR), but the role of DCs and TLR in SCD pathogenesis is unclear. Also, there are molecules contributing for enhance the endothelium dysfunction, such as homocysteine that has been associated with vascular complications in the pathology of other diseases and it may contribute to the vascular complications presented by SCD patients. Circulating microparticules (MPs) levels are augmented in several diseases and have been described in SCD, where cells membrane compounds are associated to cell’s thrombotic and coagulation state, such as tissue factor and phosphatidylserine (PS), which may contribute to endothelial dysfunction. The knowledge of all these biomarkers may contribute to new therapeutic approach discover, improveing SCD patient life quality.展开更多
文摘Sickle cell anemia (SCA) is a genetically inherited hemolytic disorder characterized by chronic inflammation. Cytokine expression affects the pivotal pathways that contribute to disease pathogenesis, but the mechanisms involved are not well understood. SCA is associated with a proinflammatory state, and an enhanced inflammatory response occurs during vasoocclusive crisis. The immune system thus plays an important role in this inflammatory condition, with several cell types secreting pro-inflammatory cytokines that contribute to the occurrence of common cyclical events in SCA patients, such as hemolysis, vascular occlusion and inflammation. Studies of these cytokines and chemokines in SCA patients have clarified the mechanisms that underlie this disease and highlighted the need for a better understanding of cytokine participation in SCA pathophysiology.
基金supported by grants from the Brazilian National Council of Research(CNPq)(3065427/2007-5 and 484457/2007-1)(M.S.G.)the Foundation of Research and Extension of Bahia(FAPESB)(1431040053063,9073/2007 and 6234/2010)(M.S.G.)and MCD/CNPq/MS-SCTIE-DECIT(409800/2006-6),(M.S.G.).
文摘Sickle cell disease (SCD) is a genetic disorder characterized by a chronic inflammatory process, and new biomarkers have been studied as promising molecules for understanding the inflammation in its pathophysiology. The hemolysis and the release of molecules associated to the hemoglobin (Hb) catabolism, such as free Hb, iron, and heme, generating a oxidant environment with production of reactive oxygen and nitrogen species. The immune system plays a very important role in the inflammation, with cells secreting pro-inflammatory cytokines and chemokines. There is also a nitric oxide (NO) resistance state, with an impaired NO bioactivity, leading to a vascular dys-function;activation of platelet, leukocytes, erythrocytes, and endothelial cells, with expression of adhesion molecules and its ligands, and several receptors, that altogether participate at inflammatory process. During inflammation, there is an increase of dendritic cells (DCs) expresse toll like receptors (TLR), but the role of DCs and TLR in SCD pathogenesis is unclear. Also, there are molecules contributing for enhance the endothelium dysfunction, such as homocysteine that has been associated with vascular complications in the pathology of other diseases and it may contribute to the vascular complications presented by SCD patients. Circulating microparticules (MPs) levels are augmented in several diseases and have been described in SCD, where cells membrane compounds are associated to cell’s thrombotic and coagulation state, such as tissue factor and phosphatidylserine (PS), which may contribute to endothelial dysfunction. The knowledge of all these biomarkers may contribute to new therapeutic approach discover, improveing SCD patient life quality.
