title: Leukocyte adhesion and the pathophysiology of sickle cell disease.
abstract: OBJECTIVE
  This article discusses the importance of leukocyte adhesion in sickle cell disease, and how this could be modulated for clinical benefit.
  
  
  RESULTS
  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 kappaB, glucocorticoids reduce activation of vascular endothelial cells, their expression of ligands for leukocyte adhesion molecules, and vaso-occlusion. Monoclonal antibodies to vascular endothelial intercellular adhesion molecule-1 inhibited hypoxia-induced vaso-occlusion in transgenic sickle mice.
  
  
  CONCLUSIONS
  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.
authors.affiliation: St Thomas' Hospital, University of London, London, UK. iheanyi.okpala@gstt.sthames.nhs.uk
authors.forename: Iheanyi
authors.initials: I
authors.lastname: Okpala
mesh_terms: D000755:Anemia, Sickle Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000986:Antisickling Agents / Q000627:therapeutic use; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D015525:Fatty Acids, Omega-3 / Q000378:metabolism* / Q000627:therapeutic use; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D000986:Antisickling Agents; D015815:Cell Adhesion Molecules; D015525:Fatty Acids, Omega-3; D005938:Glucocorticoids; D006918:Hydroxyurea