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

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.

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Vilas-Boas, W. , Cerqueira, B. , Pitanga, T. , Seixas, M. , Menezes, J. , Souza, C. , Adorno, E. and Goncalves, M. (2012) Sickle cell disease: Only one road, but different pathways for inflammation. Advances in Bioscience and Biotechnology, 3, 538-550. doi: 10.4236/abb.2012.324071.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Steinberg, M.H. (2008) Sickle Cell Anemia, the First Molecular Disease: Overview of Molecular Etiology, Pathophysiology, and Therapeutic Approaches. The Scientific World Journal, 8, 1295-1324. doi.org/10.1100/tsw.2008.157
[2] Steinberg, M.H. (2005) Predicting Clinical Severity in Sickle Cell Anaemia. British journal of haematology, 129, 465-481. doi.org/10.1111/j.1365-2141.2005.05411.x
[3] Lanaro, C., Franco-Penteado, C.F., Albuqueque, D.M., Saad, S.T., Conran, N. and Costa, F.F. (2009) Altered Levels of Cytokines and Inflammatory Mediators in Plasma and Leukocytes of Sickle Cell Anemia Patients and Effects of Hydroxyurea Therapy. Journal of leukocyte biology, 85, 235-242. doi.org/10.1189/jlb.0708445
[4] Bender, M.A. and Hobbs, W. Sickle Cell Disease. In: Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, editors. Genereviews. Seattle (WA)1993.
[5] Morris, C.R. (2011) Vascular Risk Assessment in Patients with Sickle Cell Disease. Haematologica, 96, 1-5. doi.org/10.3324/haematol.2010.035097
[6] Medina-Urrutia, A., Juarez-Rojas, J.G., Cardoso-Saldana, G., Jorge-Galarza, E., Posadas-Sanchez, R., Martinez-Alvarado, R., Caracas-Portilla, N., Mendoza Perez, E. and Posadas-Romero, C. (2011) Abnormal High-Density Lipoproteins in Overweight Adolescents with Atherogenic Dyslipidemia. Pediatrics, 127, e1521-1527.
[7] Elkind, M.S. (2006) Inflammation, Atherosclerosis, and Stroke. The neurologist, 12, 140-148. doi.org/10.1097/01.nrl.0000215789.70804.b0
[8] Thanoon, I.A., Abdul-Jabbar, H.A. and Taha, D.A. (2012) Oxidative Stress and C-Reactive Protein in Patients with Cerebrovascular Accident (Ischaemic Stroke): The Role of Ginkgo Biloba Extract. Sultan Qaboos University medical journal, 12, 197-205.
[9] Milton, J.N., Sebastiani, P., Solovieff, N., Hartley, S.W., Bhatnagar, P., Arking, D.E., Dworkis, D.A., Casella, J.F., Barron-Casella, E., Bean, C.J., Hooper, W.C., DeBaun, M.R., Garrett, M.E., Soldano, K., Telen, M.J., Ashley-Koch, A., Gladwin, M.T., Baldwin, C.T., Steinberg, M.H. and Klings, E.S. (2012) A Genome-Wide Association Study of Total Bilirubin and Cholelithiasis Risk in Sickle Cell Anemia. PloS one, 7, e34741. doi.org/10.1371/journal.pone.0034741
[10] Ebert, E.C., Nagar, M. and Hagspiel, K.D. (2010) Gastrointestinal and Hepatic Complications of Sickle Cell Disease. Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association, 8, 483-489; quiz e470.
[11] Wakugawa, Y., Kiyohara, Y., Tanizaki, Y., Kubo, M., Ninomiya, T., Hata, J., Doi, Y., Okubo, K., Oishi, Y., Shikata, K., Yonemoto, K., Maebuchi, D., Ibayashi, S. and Iida, M. (2006) C-Reactive Protein and Risk of First-Ever Ischemic and Hemorrhagic Stroke in a General Japanese Population: The Hisayama Study. Stroke; a journal of cerebral circulation, 37, 27-32. doi.org/10.1161/01.STR.0000194958.88216.87
[12] Voskaridou, E., Christoulas, D. and Terpos, E. (2012) Sickle-Cell Disease and the Heart: Review of the Current Literature. British journal of haematology, 157, 664-673.
[13] Costa, R.N., Conran, N., Albuquerque, D.M., Soares, P.H., Saad, S.T. and Costa, F.F. (2005) Association of the G-463a Myeloperoxidase Polymorphism with Infection in Sickle Cell Anemia. Haematologica, 90, 977-979.
[14] Liu, C., Xie, G., Huang, W., Yang, Y., Li, P. and Tu, Z. (2012) Elevated Serum Myeloperoxidase Activities Are Significantly Associated with the Prevalence of Acs and High Ldl-C Levels in Chd Patients. Journal of atherosclerosis and thrombosis, 19, 435-443. doi.org/10.1111/j.1365-2141.2012.09143.x
[15] Seixas, M.O., Rocha, L.C., Carvalho, M.B., Menezes, J.F., Lyra, I.M., Nascimento, V.M., Couto, R.D., Atta, A.M., Reis, M.G. and Goncalves, M.S. (2010) Levels of High-Density Lipoprotein Cholesterol (Hdl-C) among Children with Steady-State Sickle Cell Disease. Lipids in health and disease, 9, 91. doi.org/10.1186/1476-511X-9-91
[16] Wood, K.C., Hsu, L.L. and Gladwin, M.T. (2008) Sickle Cell Disease Vasculopathy: A State of Nitric Oxide Resistance. Free radical biology & medicine, 44, 1506-1528. doi.org/10.1016/j.freeradbiomed.2008.01.008
[17] Reiter, C.D., Wang, X., Tanus-Santos, J.E., Hogg, N., Cannon, R.O., 3rd, Schechter, A.N. and Gladwin, M.T. (2002) Cell-Free Hemoglobin Limits Nitric Oxide Bioavailability in Sickle-Cell Disease. Nature medicine, 8, 1383-1389. doi.org/10.1038/nm1202-799
[18] Ryter, S.W. and Tyrrell, R.M. (2000) The Heme Synthesis and Degradation Pathways: Role in Oxidant Sensitivity. Heme Oxygenase Has Both Pro- and Antioxidant Properties. Free radical biology & medicine, 28, 289-309. doi.org/10.1016/S0891-5849(99)00223-3
[19] Akinsheye, I. and Klings, E.S. (2010) Sickle Cell Anemia and Vascular Dysfunction: The Nitric Oxide Connection. Journal of cellular physiology, 224, 620-625. doi.org/10.1002/jcp.22195
[20] Villagra, J., Shiva, S., Hunter, L.A., Machado, R.F., Gladwin, M.T. and Kato, G.J. (2007) Platelet Activation in Patients with Sickle Disease, Hemolysis-Associated Pulmonary Hypertension, and Nitric Oxide Scavenging by Cell-Free Hemoglobin. Blood, 110, 2166-2172. doi.org/10.1182/blood-2006-12-061697
[21] Spiecker, M., Darius, H., Kaboth, K., Hubner, F. and Liao, J.K. (1998) Differential Regulation of Endothelial Cell Adhesion Molecule Expression by Nitric Oxide Donors and Antioxidants. Journal of leukocyte biology, 63, 732-739.
[22] Aslan, M., Ryan, T.M., Adler, B., Townes, T.M., Parks, D.A., Thompson, J.A., Tousson, A., Gladwin, M.T., Patel, R.P., Tarpey, M.M., Batinic-Haberle, I., White, C.R. and Freeman, B.A. (2001) Oxygen Radical Inhibition of Nitric Oxide-Dependent Vascular Function in Sickle Cell Disease. Proceedings of the National Academy of Sciences of the United States of America, 98, 15215-15220. doi.org/10.1073/pnas.221292098
[23] Solovey, A., Kollander, R., Milbauer, L.C., Abdulla, F., Chen, Y., Kelm, R.J., Jr. and Hebbel, R.P. (2010) Endothelial Nitric Oxide Synthase and Nitric Oxide Regulate Endothelial Tissue Factor Expression in Vivo in the Sickle Transgenic Mouse. American journal of hematology, 85, 41-45.
[24] Jain, S. and Gladwin, M.T. (2010) Arginine Metabolism and Nitric Oxide Bioavailability in Sickle Cell Disease. Journal of pediatric hematology/oncology, 32, e247-248. doi.org/10.1097/MPH.0b013e3181ec0b00
[25] Zhou, Z., Behymer, M. and Guchhait, P. (2011) Role of Extracellular Hemoglobin in Thrombosis and Vascular Occlusion in Patients with Sickle Cell Anemia. Anemia, 2011, 918916. doi.org/10.1155/2011/918916
[26] Morris, C.R., Kato, G.J., Poljakovic, M., Wang, X., Blackwelder, W.C., Sachdev, V., Hazen, S.L., Vichinsky, E.P., Morris, S.M., Jr. and Gladwin, M.T. (2005) Dysregulated Arginine Metabolism, Hemolysis-Associated Pulmonary Hypertension, and Mortality in Sickle Cell Disease. JAMA: the journal of the American Medical Association, 294, 81-90. doi.org/10.1001/jama.294.1.81
[27] Vilas-Boas, W., Cerqueira, B.A., Zanette, A.M., Reis, M.G., Barral-Netto, M. and Goncalves, M.S. (2010) Arginase Levels and Their Association with Th17-Related Cytokines, Soluble Adhesion Molecules (Sicam-1 and Svcam-1) and Hemolysis Markers among Steady-State Sickle Cell Anemia Patients. Annals of hematology, 89, 877-882. doi.org/10.1007/s00277-010-0954-9
[28] Bialecka, M., Robowski, P., Honczarenko, K., Roszmann, A. and Slawek, J. (2009) Genetic and Environmental Factors for Hyperhomocysteinaemia and Its Clinical Implications in Parkinson's Disease. Neurologia i neurochirurgia polska, 43, 272-285.
[29] Refsum, H., Ueland, P.M., Nygard, O. and Vollset, S.E. (1998) Homocysteine and Cardiovascular Disease. Annual review of medicine, 49, 31-62. doi.org/10.1146/annurev.med.49.1.31
[30] Clarke, R., Daly, L., Robinson, K., Naughten, E., Cahalane, S., Fowler, B. and Graham, I. (1991) Hyperhomocysteinemia: An Independent Risk Factor for Vascular Disease. The New England journal of medicine, 324, 1149-1155. doi.org/10.1056/NEJM199104253241701
[31] Lowenthal, E.A., Mayo, M.S., Cornwell, P.E. and Thornley-Brown, D. (2000) Homocysteine Elevation in Sickle Cell Disease. Journal of the American College of Nutrition, 19, 608-612.
[32] Siniscalchi, A., Mancuso, F., Gallelli, L., Ferreri Ibbadu, G., Biagio Mercuri, N. and De Sarro, G. (2005) Increase in Plasma Homocysteine Levels Induced by Drug Treatments in Neurologic Patients. Pharmacological research: the official journal of the Italian Pharmacological Society, 52, 367-375.
[33] Dudman, N.P., Temple, S.E., Guo, X.W., Fu, W. and Perry, M.A. (1999) Homocysteine Enhances Neutrophil-Endothelial Interactions in Both Cultured Human Cells and Rats in Vivo. Circulation research, 84, 409-416. doi.org/10.1161/01.RES.84.4.409
[34] Chies, J.A. and Nardi, N.B. (2001) Sickle Cell Disease: A Chronic Inflammatory Condition. Medical hypotheses, 57, 46-50. doi.org/10.1054/mehy.2000.1310
[35] Wallace, K.L. and Linden, J. (2010) Adenosine A2a Receptors Induced on Inkt and Nk Cells Reduce Pulmonary Inflammation and Injury in Mice with Sickle Cell Disease. Blood, 116, 5010-5020. doi.org/10.1182/blood-2010-06-290643
[36] Park, S.W., Kim, M., Brown, K.M., D'Agati, V.D. and Lee, H.T. (2011) Paneth Cell-Derived Interleukin-17a Causes Multiorgan Dysfunction after Hepatic Ischemia and Reperfusion Injury. Hepatology, 53, 1662-1675. doi.org/10.1002/hep.24253
[37] Chen, G.Y. and Nunez, G. (2010) Sterile Inflammation: Sensing and Reacting to Damage. Nature reviews. Immunology, 10, 826-837. doi.org/10.1038/nri2873
[38] Akira, S., Uematsu, S. and Takeuchi, O. (2006) Pathogen Recognition and Innate Immunity. Cell, 124, 783-801. doi.org/10.1016/j.cell.2006.02.015
[39] Iwasaki, A. and Medzhitov, R. (2004) Toll-Like Receptor Control of the Adaptive Immune Responses. Nature immunology, 5, 987-995. doi.org/10.1038/ni1112
[40] Pulendran, B. (2005) Variegation of the Immune Response with Dendritic Cells and Pathogen Recognition Receptors. Journal of immunology, 174, 2457-2465.
[41] 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
[42] Gregory, S., Zilber, M., Charron, D. and Gelin, C. (2000) Human Cd1a Molecule Expressed on Monocytes Plays an Accessory Role in the Superantigen-Induced Activation of T Lymphocytes. Human immunology, 61, 193-201. doi.org/10.1016/S0198-8859(99)00129-9
[43] Sloma, I., Zilber, M.T., Charron, D., Girot, R., Tamouza, R. and Gelin, C. (2004) Upregulation and Atypical Expression of the Cd1 Molecules on Monocytes in Sickle Cell Disease. Human immunology, 65, 1370-1376. doi.org/10.1016/j.humimm.2004.09.009
[44] Urban, B.C., Shafi, M.J., Cordery, D.V., Macharia, A., Lowe, B., Marsh, K. and Williams, T.N. (2006) Frequencies of Peripheral Blood Myeloid Cells in Healthy Kenyan Children with Alpha+ Thalassemia and the Sickle Cell Trait. The American journal of tropical medicine and hygiene, 74, 578-584
[45] Krishnegowda, G., Hajjar, A.M., Zhu, J., Douglass, E.J., Uematsu, S., Akira, S., Woods, A.S. and Gowda, D.C. (2005) Induction of Proinflammatory Responses in Macrophages by the Glycosylphosphatidylinositols of Plasmodium Falciparum: Cell Signaling Receptors, Glycosylphosphatidylinositol (Gpi) Structural Requirement, and Regulation of Gpi Activity. The Journal of biological chemistry, 280, 8606-8616. doi.org/10.1074/jbc.M413541200
[46] Pichyangkul, S., Yongvanitchit, K., Kum-arb, U., Hemmi, H., Akira, S., Krieg, A.M., Heppner, D.G., Stewart, V.A., Hasegawa, H., Looareesuwan, S., Shanks, G.D. and Miller, R.S. (2004) Malaria Blood Stage Parasites Activate Human Plasmacytoid Dendritic Cells and Murine Dendritic Cells through a Toll-Like Receptor 9-Dependent Pathway. Journal of immunology, 172, 4926-4933.
[47] Lorenz, E., Mira, J.P., Frees, K.L. and Schwartz, D.A. (2002) Relevance of Mutations in the Tlr4 Receptor in Patients with Gram-Negative Septic Shock. Archives of internal medicine, 162, 1028-1032. doi.org/10.1001/archinte.162.9.1028
[48] Khansari, N., Shakiba, Y. and Mahmoudi, M. (2009) Chronic Inflammation and Oxidative Stress as a Major Cause of Age-Related Diseases and Cancer. Recent patents on inflammation & allergy drug discovery, 3, 73-80. doi.org/10.2174/187221309787158371
[49] Valdivia, P.A., Zenteno-Savin, T., Gardner, S.C. and Aguirre, A.A. (2007) Basic Oxidative Stress Metabolites in Eastern Pacific Green Turtles (Chelonia Mydas Agassizii). Comparative biochemistry and physiology. Toxicology & pharmacology: CBP, 146, 111-117.
[50] Inoue, M., Sato, E.F., Nishikawa, M., Park, A.M., Kira, Y., Imada, I. and Utsumi, K. (2003) Mitochondrial Generation of Reactive Oxygen Species and Its Role in Aerobic Life. Current medicinal chemistry, 10, 2495-2505. doi.org/10.2174/0929867033456477
[51] Akopova, O.V., Kolchinskaya, L.I., Nosar, V.I., Bouryi, V.A., Mankovska, I.N. and Sagach, V.F. (2012) Cytochrome C as an Amplifier of Ros Release in Mitochondria. Fiziolohichnyi zhurnal, 58, 3-12.
[52] Gutteridge, J.M., Rowley, D.A. and Halliwell, B. (1982) Superoxide-Dependent Formation of Hydroxyl Radicals and Lipid Peroxidation in the Presence of Iron Salts. Detection of 'Catalytic' Iron and Anti-Oxidant Activity in Extracellular Fluids. The Biochemical journal, 206, 605-609.
[53] Wickens, A.P. (2001) Ageing and the Free Radical Theory. Respiration physiology, 128, 379-391. doi.org/10.1016/S0034-5687(01)00313-9
[54] Conner, E.M. and Grisham, M.B. (1996) Inflammation, Free Radicals, and Antioxidants. Nutrition, 12, 274-277. doi.org/10.1016/S0899-9007(96)00000-8
[55] Mateos, R. and Bravo, L. (2007) Chromatographic and Electrophoretic Methods for the Analysis of Biomarkers of Oxidative Damage to Macromolecules (DNA, Lipids, and Proteins). Journal of separation science, 30, 175-191. doi.org/10.1002/jssc.200600314
[56] Pastore, A., Federici, G., Bertini, E. and Piemonte, F. (2003) Analysis of Glutathione: Implication in Redox and Detoxification. Clinica chimica acta; international journal of clinical chemistry, 333, 19-39.
[57] Esposito, K., Ciotola, M., Schisano, B., Misso, L., Giannetti, G., Ceriello, A. and Giugliano, D. (2006) Oxidative Stress in the Metabolic Syndrome. Journal of endocrinological investigation, 29, 791-795.
[58] Peterhans, E. (1997) Reactive Oxygen Species and Nitric Oxide in Viral Diseases. Biological trace element research, 56, 107-116. doi.org/10.1007/BF02778986
[59] Stehbens, W.E. (2003) Oxidative Stress, Toxic Hepatitis, and Antioxidants with Particular Emphasis on Zinc. Experimental and molecular pathology, 75, 265-276. doi.org/10.1016/S0014-4800(03)00097-2
[60] Emmendoerffer, A., Hecht, M., Boeker, T., Mueller, M. and Heinrich, U. (2000) Role of Inflammation in Chemical-Induced Lung Cancer. Toxicology letters, 112-113, 185-191. doi.org/10.1016/S0378-4274(99)00285-4
[61] Segal, A.W. (2006) How Superoxide Production by Neutrophil Leukocytes Kills Microbes. Novartis Foundation symposium, 279, 92-98; discussion 98-100, 216-109.
[62] Costa, A.D. and Garlid, K.D. (2008) Intramitochondrial Signaling: Interactions among Mitokatp, Pkcepsilon, Ros, and Mpt. American journal of physiology. Heart and circulatory physiology, 295, H874-882. doi.org/10.1152/ajpheart.01189.2007
[63] Fialkow, L., Wang, Y. and Downey, G.P. (2007) Reactive Oxygen and Nitrogen Species as Signaling Molecules Regulating Neutrophil Function. Free radical biology & medicine, 42, 153-164. doi.org/10.1016/j.freeradbiomed.2006.09.030
[64] Hebbel, R.P. and Vercellotti, G.M. (1997) The Endothelial Biology of Sickle Cell Disease. The Journal of laboratory and clinical medicine, 129, 288-293. doi.org/10.1016/S0022-2143(97)90176-1
[65] Kaul, D.K. and Hebbel, R.P. (2000) Hypoxia/Reoxygenation Causes Inflammatory Response in Transgenic Sickle Mice but Not in Normal Mice. The Journal of clinical investigation, 106, 411-420. doi.org/10.1172/JCI9225
[66] Osarogiagbon, U.R., Choong, S., Belcher, J.D., Vercellotti, G.M., Paller, M.S. and Hebbel, R.P. (2000) Reperfusion Injury Pathophysiology in Sickle Transgenic Mice. Blood, 96, 314-320.
[67] Stuart, M.J. and Setty, B.N. (2001) Acute Chest Syndrome of Sickle Cell Disease: New Light on an Old Problem. Current opinion in hematology, 8, 111-122. doi.org/10.1097/00062752-200103000-00009
[68] Nath, K.A., Grande, J.P., Croatt, A.J., Frank, E., Caplice, N.M., Hebbel, R.P. and Katusic, Z.S. (2005) Transgenic Sickle Mice Are Markedly Sensitive to Renal Ischemia-Reperfusion Injury. The American journal of pathology, 166, 963-972. doi.org/10.1016/S0002-9440(10)62318-8
[69] Nagababu, E., Fabry, M.E., Nagel, R.L. and Rifkind, J.M. (2008) Heme Degradation and Oxidative Stress in Murine Models for Hemoglobinopathies: Thalassemia, Sickle Cell Disease and Hemoglobin C Disease. Blood cells, molecules & diseases, 41, 60-66. doi.org/10.1016/j.bcmd.2007.12.003
[70] Nur, E., Biemond, B.J., Otten, H.M., Brandjes, D.P., Schnog, J.J. and Group, C.S. (2011) Oxidative Stress in Sickle Cell Disease; Pathophysiology and Potential Implications for Disease Management. American journal of hematology, 86, 484-489. doi.org/10.1002/ajh.22012
[71] Repka, T. and Hebbel, R.P. (1991) Hydroxyl Radical Formation by Sickle Erythrocyte Membranes: Role of Pathologic Iron Deposits and Cytoplasmic Reducing Agents. Blood, 78, 2753-2758.
[72] Setty, B.N., Rao, A.K. and Stuart, M.J. (2001) Thrombophilia in Sickle Cell Disease: The Red Cell Connection. Blood, 98, 3228-3233. doi.org/10.1182/blood.V98.12.3228
[73] Francis, R.B., Jr. and Haywood, L.J. (1992) Elevated Immunoreactive Tumor Necrosis Factor and Interleukin-1 in Sickle Cell Disease. Journal of the National Medical Association, 84, 611-615.
[74] Aslan, M., Thornley-Brown, D. and Freeman, B.A. (2000) Reactive Species in Sickle Cell Disease. Annals of the New York Academy of Sciences, 899, 375-391. doi.org/10.1111/j.1749-6632.2000.tb06201.x
[75] Gladwin, M.T., Schechter, A.N., Ognibene, F.P., Coles, W.A., Reiter, C.D., Schenke, W.H., Csako, G., Waclawiw, M.A., Panza, J.A. and Cannon, R.O., 3rd. (2003) Divergent Nitric Oxide Bioavailability in Men and Women with Sickle Cell Disease. Circulation, 107, 271-278. doi.org/10.1161/01.CIR.0000044943.12533.A8
[76] Selvaraj, S.K., Giri, R.K., Perelman, N., Johnson, C., Malik, P. and Kalra, V.K. (2003) Mechanism of Monocyte Activation and Expression of Proinflammatory Cytochemokines by Placenta Growth Factor. Blood, 102, 1515-1524. doi.org/10.1182/blood-2002-11-3423
[77] Musa, B.O., Onyemelukwe, G.C., Hambolu, J.O., Mamman, A.I. and Isa, A.H. (2010) Pattern of Serum Cytokine Expression and T-Cell Subsets in Sickle Cell Disease Patients in Vaso-Occlusive Crisis. Clinical and vaccine immunology: CVI, 17, 602-608. doi.org/10.1128/CVI.00145-09
[78] Goossens, V., Grooten, J., De Vos, K. and Fiers, W. (1995) Direct Evidence for Tumor Necrosis Factor-Induced Mitochondrial Reactive Oxygen Intermediates and Their Involvement in Cytotoxicity. Proceedings of the National Academy of Sciences of the United States of America, 92, 8115-8119. doi.org/10.1073/pnas.92.18.8115
[79] Muhl, D., Woth, G., Drenkovics, L., Varga, A., Ghosh, S., Csontos, C., Bogar, L., Weber, G. and Lantos, J. (2011) Comparison of Oxidative Stress & Leukocyte Activation in Patients with Severe Sepsis & Burn Injury. The Indian journal of medical research, 134, 69-78.
[80] Read, M.A., Whitley, M.Z., Williams, A.J. and Collins, T. (1994) Nf-Kappa B and I Kappa B Alpha: An Inducible Regulatory System in Endothelial Activation. The Journal of experimental medicine, 179, 503-512. doi.org/10.1084/jem.179.2.503
[81] Patel, S.J., Jindal, R., King, K.R., Tilles, A.W. and Yarmush, M.L. (2011) The Inflammatory Response to Double Stranded DNA in Endothelial Cells Is Mediated by Nfkappab and Tnfalpha. PloS one, 6, e19910. doi.org/10.1371/journal.pone.0019910
[82] Croizat, H. (1994) Circulating Cytokines in Sickle Cell Patients During Steady State. British journal of haematology, 87, 592-597. doi.org/10.1111/j.1365-2141.1994.tb08318.x
[83] Raghupathy, R., Haider, M.Z., Azizieh, F., Abdelsalam, R., D'Souza, T.M. and Adekile, A.D. (2000) Th1 and Th2 Cytokine Profiles in Sickle Cell Disease. Acta haematologica, 103, 197-202. doi.org/10.1159/000041049
[84] Goncalves, M.S., Queiroz, I.L., Cardoso, S.A., Zanetti, A., Strapazoni, A.C., Adorno, E., Albuquerque, A., Sant'Ana, A., dos Reis, M.G., Barral, A. and Barral Netto, M. (2001) Interleukin 8 as a Vaso-Occlusive Marker in Brazilian Patients with Sickle Cell Disease. Brazilian journal of medical and biological research, 34, 1309-1313.
[85] Pathare, A., Al Kindi, S., Alnaqdy, A.A., Daar, S., Knox-Macaulay, H. and Dennison, D. (2004) Cytokine Profile of Sickle Cell Disease in Oman. American journal of hematology, 77, 323-328. doi.org/10.1002/ajh.20196
[86] Akohoue, S.A., Shankar, S., Milne, G.L., Morrow, J., Chen, K.Y., Ajayi, W.U. and Buchowski, M.S. (2007) Energy Expenditure, Inflammation, and Oxidative Stress in Steady-State Adolescents with Sickle Cell Anemia. Pediatric research, 61, 233-238. doi.org/10.1203/pdr.0b013e31802d7754
[87] Lard, L.R., Mul, F.P., de Haas, M., Roos, D. and Duits, A.J. (1999) Neutrophil Activation in Sickle Cell Disease. Journal of leukocyte biology, 66, 411-415.
[88] Okpala, I. (2002) Steady-State Platelet Count and Complications of Sickle Cell Disease. The hematology journal: the official journal of the European Haematology Association / EHA, 3, 214-215.
[89] Schnog, J.B., Rojer, R.A., Mac Gillavry, M.R., Ten Cate, H., Brandjes, D.P. and Duits, A.J. (2003) Steady-State Svcam-1 Serum Levels in Adults with Sickle Cell Disease. Annals of hematology, 82, 109-113.
[90] Dworkis, D.A., Klings, E.S., Solovieff, N., Li, G., Milton, J.N., Hartley, S.W., Melista, E., Parente, J., Se-bastiani, P., Steinberg, M.H. and Baldwin, C.T. (2011) Severe Sickle Cell Anemia Is Associated with Increased Plasma Levels of Tnf-R1 and Vcam-1. American journal of hematology, 86, 220-223. doi.org/10.1002/ajh.21928
[91] Cerqueira, B.A., Boas, W.V., Zanette, A.D., Reis, M.G. and Goncalves, M.S. (2011) Increased Concentrations of Il-18 and Uric Acid in Sickle Cell Anemia: Contribution of Hemolysis, Endothelial Activation and the Inflammasome. Cytokine, 56, 471-476. doi.org/10.1016/j.cyto.2011.08.013
[92] Berry, C.E. and Hare, J.M. (2004) Xanthine Oxidoreductase and Cardiovascular Disease: Molecular Mechanisms and Pathophysiological Implications. The Journal of physiology, 555, 589-606. doi.org/10.1113/jphysiol.2003.055913
[93] Xu, P., Huecksteadt, T.P. and Hoidal, J.R. (1996) Molecular Cloning and Characterization of the Human Xanthine Dehydrogenase Gene (Xdh). Genomics, 34, 173-180. doi.org/10.1006/geno.1996.0262
[94] Zhang, C., Hein, T.W., Wang, W., Ren, Y., Shipley, R.D. and Kuo, L. (2006) Activation of Jnk and Xanthine Oxidase by Tnf-Alpha Impairs Nitric Oxide-Mediated Dilation of Coronary Arterioles. Journal of molecular and cellular cardiology, 40, 247-257. doi.org/10.1016/j.yjmcc.2005.11.010
[95] Martinon, F., Mayor, A. and Tschopp, J. (2009) The Inflammasomes: Guardians of the Body. Annual review of immunology, 27, 229-265. doi.org/10.1146/annurev.immunol.021908.132715
[96] Martinon, F., Petrilli, V., Mayor, A., Tardivel, A. and Tschopp, J. (2006) Gout-Associated Uric Acid Crystals Activate the Nalp3 Inflammasome. Nature, 440, 237-241. doi.org/10.1038/nature04516
[97] Vieira-de-Abreu, A., Campbell, R.A., Weyrich, A.S. and Zimmerman, G.A. (2012) Platelets: Versatile Effector Cells in Hemostasis, Inflammation, and the Immune Continuum. Seminars in immunopathology, 34, 5-30. doi.org/10.1007/s00281-011-0286-4
[98] Maugeri, N., Baldini, M., Ramirez, G.A., Rovere-Querini, P. and Manfredi, A.A. (2012) Platelet-Leukocyte Deregulated Interactions Foster Sterile Inflammation and Tissue Damage in Immune-Mediated Vessel Diseases. Thrombosis research, 129, 267-273. doi.org/10.1016/j.thromres.2011.12.001
[99] Stokes, K.Y. and Granger, D.N. (2012) Platelets: A Critical Link between Inflammation and Microvascular Dysfunction. The Journal of physiology, 590, 1023-1034.
[100] Chiang, E.Y. and Frenette, P.S. (2005) Sickle Cell Vaso-Occlusion. Hematology/oncology clinics of North America, 19, 771-784, v. doi.org/10.1016/j.hoc.2005.08.002
[101] Charneski, L. and Congdon, H.B. (2010) Effects of Antiplatelet and Anticoagulant Medications on the Vasoocclusive and Thrombotic Complications of Sickle Cell Disease: A Review of the Literature. American journal of health-system pharmacy: AJHP: official journal of the American Society of Health-System Pharmacists, 67, 895-900.
[102] May, A.E., Seizer, P. and Gawaz, M. (2008) Platelets: Inflammatory Firebugs of Vascular Walls. Arteriosclerosis, thrombosis, and vascular biology, 28, s5-10. doi.org/10.1161/ATVBAHA.107.158915
[103] Gawaz, M., Langer, H. and May, A.E. (2005) Platelets in Inflammation and Atherogenesis. The Journal of clinical investigation, 115, 3378-3384. doi.org/10.1172/JCI27196
[104] Polanowska-Grabowska, R., Wallace, K., Field, J.J., Chen, L., Marshall, M.A., Figler, R., Gear, A.R. and Linden, J. (2010) P-Selectin-Mediated Platelet-Neutrophil Aggregate Formation Activates Neutrophils in Mouse and Human Sickle Cell Disease. Arteriosclerosis, thrombosis, and vascular biology, 30, 2392-2399. doi.org/10.1161/ATVBAHA.110.211615
[105] Lee, S.P., Ataga, K.I., Orringer, E.P., Phillips, D.R. and Parise, L.V. (2006) Biologically Active Cd40 Ligand Is Elevated in Sickle Cell Anemia: Potential Role for Platelet-Mediated Inflammation. Arteriosclerosis, thrombosis, and vascular biology, 26, 1626-1631. doi.org/10.1161/01.ATV.0000220374.00602.a2
[106] Wolf, P. (1967) The Nature and Significance of Platelet Products in Human Plasma. British journal of haematology, 13, 269-288. doi.org/10.1111/j.1365-2141.1967.tb08741.x
[107] Amabile, N., Guerin, A.P., Leroyer, A., Mallat, Z., Nguyen, C., Boddaert, J., London, G.M., Tedgui, A. and Boulanger, C.M. (2005) Circulating Endothelial Microparticles Are Associated with Vascular Dysfunction in Patients with End-Stage Renal Failure. Journal of the American Society of Nephrology: JASN, 16, 3381-3388. doi.org/10.1681/ASN.2005050535
[108] Piccin, A., Murphy, W.G. and Smith, O.P. (2007) Circulating Microparticles: Pathophysiology and Clinical Implications. Blood reviews, 21, 157-171. doi.org/10.1016/j.blre.2006.09.001
[109] Cocucci, E., Racchetti, G. and Meldolesi, J. (2009) Shedding Microvesicles: Artefacts No More. Trends in cell biology, 19, 43-51. doi.org/10.1016/j.tcb.2008.11.003
[110] Ardoin, S.P., Shanahan, J.C. and Pisetsky, D.S. (2007) The Role of Microparticles in Inflammation and Thrombosis. Scandinavian journal of immunology, 66, 159-165. doi.org/10.1111/j.1365-3083.2007.01984.x
[111] van Tits, L.J., van Heerde, W.L., Landburg, P.P., Boderie, M.J., Muskiet, F.A., Jacobs, N., Duits, A.J. and Schnog, J.B. (2009) Plasma Annexin A5 and Microparticle Phosphatidylserine Levels Are Elevated in Sickle Cell Disease and Increase Further During Painful Crisis. Biochemical and biophysical research communications, 390, 161-164. doi.org/10.1016/j.bbrc.2009.09.102
[112] Noubouossie, D.C., Le, P.Q., Rozen, L., Debaugnies, F., Ferster, A. and Demulder, A. (2011) Evaluation of the Procoagulant Activity of Endogenous Phospholipids in the Platelet-Free Plasma of Children with Sickle Cell Disease Using Functional Assays. Thrombosis research. doi.org/10.1016/j.thromres.2011.10.016
[113] Shet, A.S., Aras, O., Gupta, K., Hass, M.J., Rausch, D.J., Saba, N., Koopmeiners, L., Key, N.S. and Hebbel, R.P. (2003) Sickle Blood Contains Tissue Factor-Positive Microparticles Derived from Endothelial Cells and Monocytes. Blood, 102, 2678-2683. doi.org/10.1182/blood-2003-03-0693
[114] Ataga, K.I., Brittain, J.E., Desai, P., May, R., Jones, S., Delaney, J., Strayhorn, D., Hinderliter, A. and Key, N.S. (2012) Association of Coagulation Activation with Clinical Complications in Sickle Cell Disease. PloS one, 7, e29786. doi.org/10.1371/journal.pone.0029786
[115] Mahfoudhi, E., Lecluse, Y., Driss, F., Abbes, S., Flaujac, C. and Garcon, L. (2012) Red Cells Exchanges in Sickle Cells Disease Lead to a Selective Reduction of Erythrocytes-Derived Blood Microparticles. British journal of haematology, 156, 545-547. doi.org/10.1111/j.1365-2141.2011.08897.x
[116] van Beers, E.J., Schaap, M.C., Berckmans, R.J., Nieuwland, R., Sturk, A., van Doormaal, F.F., Meijers, J.C., Biemond, B.J. and group, C.s. (2009) Circulating Erythrocyte-Derived Microparticles Are Associated with Coagulation Activation in Sickle Cell Disease. Haematologica, 94, 1513-1519. doi.org/10.3324/haematol.2009.008938
[117] Michelson, A.D., Rajasekhar, D., Bednarek, F.J. and Barnard, M.R. (2000) Platelet and Platelet-Derived Microparticle Surface Factor V/Va Binding in Whole Blood: Differences between Neonates and Adults. Thrombosis and haemostasis, 84, 689-694.
[118] Adedeji, M.O., Cespedes, J., Allen, K., Subramony, C. and Hughson, M.D. (2001) Pulmonary Thrombotic Arteriopathy in Patients with Sickle Cell Disease. Archives of pathology & laboratory medicine, 125, 1436-1441.

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