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01.Sickle Cell Hemoglobinopathy And Sudden Death (pp. 125-130)
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Sickle Cell Crisis And Malaria The Band 3 Connection (pp. 99-112) $25.00
Authors:  Kennedy, J. Randall (Manatee Memorial Hospital)
Abstract:
The severity of the vaso-occlusive process that characterizes a sickle cell crisis would seem to be an irreversible one but it usually resolves with only symptomatic treatment. This reversibility suggests a precarious balance between an erythrocyte adhesive process and an equally energetic anti-occlusive mechanism. This paper presents a hypothesis addressing this duality that evolved from consideration of the ability of the sickle trait to prevent the similar and equally deleterious vaso-occlusion pathology that occurs in falciparum malaria. The malaria benefit is thought to be the result of natural antibodies whose normal function is to eliminate senescent red cells that display band 3 clusters on their surface. These band 3 clusters also appear on malaria infected and sickle cells. It is proposed that prematurely denatured sickle hemoglobin in sickle trait erythrocytes is responsible for generating the band 3 clusters that evoke the antibody response that benefits a malaria patient. The presence of an even greater abundance of these clusters and their antibodies in sickle cell disease is proposed as a major factor in both the cause and of the resolution of a sickle crisis. Sickle erythrocytes and malaria infected erythrocytes that display band 3 clusters adhere to endothelial CD36 and thrombospondin molecules and this adhesion can be prevented by certain band 3 peptides and by antibodies that recognize these peptides. If natural band 3 specific antibodies block adhesion to both CD36 and thrombospondin they will not only prevent adhesion of erythrocytes bearing these clusters, they will also disrupt the CD36 thrombospondin bridge that helps reticulocytes to adhere to the endothelium. These antibodies exist and their proposed up-regulation in sickle cell disease and malaria suggests a therapeutic potential that deserves further investigation. 


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Sickle Cell Crisis And Malaria The Band 3 Connection (pp. 99-112)