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Ferwerda, B., McCall, M.B., Alonso, S., Giamarellos-Bourboulis, E.J., Mouktaroudi, M., Izagirre, N., Syafruddin, D., Kibiki, G., Cristea, T., Hijmans, A., Hamann, L., Israel, S., ElGhazali, G., Troye-Blomberg, M., Kumpf, O., Maiga, B., Dolo, A., Doumbo, O., Hermsen, C.C., Stalenhoef, A.F., van Crevel, R., Brunner, H.G., Oh, D.Y., Schumann, R.R., de la Rua, C., Sauerwein, R., Kullberg, B.J., van der Ven, A.J., van der Meer, J.W. and Netea, M.G. (2007) Tlr4 Polymorphisms, Infectious Diseases, and Evolutionary

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• TITLE: Sickle cell disease: Only one road, but different pathways for inflammation

  AUTHORS: Wendell Vilas-Boas, Bruno Antônio Veloso Cerqueira, Thassila Nogueira Pitanga, Magda Oliveira Seixas, Joelma Menezes, Cyntia Cajado de Souza, Elisângela Vitória Adorno, Marilda Souza Goncalves

  KEYWORDS: Sickle Cell Disease; Inflammation; Oxidative Stress; Cells Activation

  JOURNAL NAME: Advances in Bioscience and Biotechnology, Vol.3 No.4A, August 24, 2012

  ABSTRACT: 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.