title: Blood mononuclear cells and platelets have abnormal fatty acid composition in homozygous sickle cell disease.
abstract: Leukocyte adhesion to vascular endothelium contributes to vaso-occlusion and widespread organ damage in sickle cell disease (SCD). Previously, we found high expression of the adhesion molecules alphaMbeta2 integrin and L-selectin in HbSS individuals with severe disease. Since membrane n-6 and n-3 polyunsaturated fatty acids modulate cell adhesion, inflammation, aggregation and vascular tone, we investigated the fatty acid composition of mononuclear cells (MNC) and platelets of HbSS patients in steady state (n=28) and racially matched, healthy HbAA controls with similar age and sex distribution living in the same environment (n=13). MNC phospholipids of the patients had lower levels of docosahexaenoic acid (DHA, p<0.01) and increased arachidonic acid (AA, p<0.005) relative to HbAA controls. Similarly, platelets from HbSS patients had less eicosapentaenoic acid (EPA, p<0.05) and more AA (p<0.05) in choline phosphoglycerides (CPG), with reduced DHA (p<0.05) in ethanolamine phosphoglycerides. Platelet CPG had lower DHA levels in SCD patients with complications compared to those without (p<0.05). Reduced cell content of EPA and DHA relative to AA favours the production of aggregatory and proinflammatory eicosanoids that activate leukocytes and platelets. This facilitates inflammation, leukocyte adhesion, platelet aggregation and vaso-occlusion in SCD.
authors.affiliation: Institute of Brain Chemistry and Human Nutrition, London Metropolitan University and Department of Hematology, St. Thomas' Hospital, London, UK.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Ren
authors.forename: Iheanyi
authors.initials: I
authors.lastname: Okpala
authors.forename: Kebreab
authors.initials: K
authors.lastname: Ghebremeskel
authors.forename: Cynthia C
authors.initials: CC
authors.lastname: Ugochukwu
authors.forename: Obike
authors.initials: O
authors.lastname: Ibegbulam
authors.forename: Michael
authors.initials: M
authors.lastname: Crawford
mesh_terms: D000328:Adult; D000368:Aged; D000755:Anemia, Sickle Cell / Q000097:blood*; D016718:Arachidonic Acid / Q000032:analysis; D001773:Blood Cells / Q000737:chemistry; D001792:Blood Platelets / Q000737:chemistry* / Q000473:pathology; D016022:Case-Control Studies; D002448:Cell Adhesion; D004281:Docosahexaenoic Acids / Q000032:analysis; D015118:Eicosapentaenoic Acid / Q000032:analysis; D005227:Fatty Acids / Q000032:analysis*; D006720:Homozygote; D006801:Humans; D007249:Inflammation; D007963:Leukocytes, Mononuclear / Q000737:chemistry* / Q000473:pathology; D008875:Middle Aged; D010713:Phosphatidylcholines / Q000032:analysis; D010743:Phospholipids / Q000032:analysis
chemical_list: D005227:Fatty Acids; D010713:Phosphatidylcholines; D010743:Phospholipids; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid