期刊
CURRENT OPINION IN HEMATOLOGY
卷 13, 期 1, 页码 40-44出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.moh.0000190108.62414.06
关键词
adhesion; leukocytes; sickle cell disease
类别
Purpose of review. This article discusses the importance of leukocyte adhesion in sickle cell disease, and how this could be modulated for clinical benefit. Recent findings. Recurrent inflammation and vasculopathy occur in sickle cell disease. As a result, leukocytes and vascular endothelial cells are activated and increase their expression of adhesion molecules. Adhesion of leukocytes to other blood cells and endothelium contributes to vaso-occlusion in sickle cell disease. High-level expression of adhesion molecules by leukocytes is associated with clinically severe disease. Pancellular membrane lipid abnormalities, including reduced proportions of omega-3 fatty acids, occur in sickle cell disease. These lipid abnormalities are more severe in patients with disease complications and in those with a greater degree of anaemia. Since lipid constitution of cell membranes affects surface expression of adhesion molecules, the above findings could account for earlier observations that omega-3 fatty acids reduce P-selectin expression and reduce the frequency of sickle cell crisis. By inhibition of nuclear factor kappa B, glucocorticoids reduce activation of vascular endothelial cells, their expression of ligands for leukocyte adhesion molecules, and vasoocclusion. Monoclonal antibodies to vascular endothelial intercellular adhesion molecule-1 inhibited hypoxia-induced vaso-occlusion in transgenic sickle mice. Summary. Although hydroxyurea and glucocorticoids reduce adhesion molecule expression by leukocytes and vascular endothelial cells, cytotoxicity and systemic side effects dampen enthusiasm for their use in sickle cell disease. Omega-3 fatty acids have shown promising efficacy and safety in pilot studies. A large clinical trial of these naturally occurring substances is required.
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