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Okpala, Iheanyi, Ren, Hongmei, Ghebremeskel, Kebreab, Ugochukwu, Cynthia C., Ibegbulam, Obike and Crawford, Michael A. (2004) Blood mononuclear cells and platelets have abnormal fatty acid composition in homozygous sickle cell disease. Blood, 104 (11). ISSN 0006-4971
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 αMβ2 integrin and L-selectin in HbSS individuals with severe disease. The n-6 and n-3 polyunsaturated fatty acids (FA) are vital structural and functional components of cell and sub-cellular membranes. They modulate cell adhesion, inflammation, aggregation and vascular tone. We investigated the FA composition of mononuclear cells (MNC) and platelets of HbSS patients in steady-state (n = 28); and racially matched, healthy HbAA controls (n = 13). MNC phospholipids of the patients had low levels of docosahexanoic acid (DHA, p<0.01), n-3 metabolites (p<0.05) and total n-3 polyunsaturated FA (p<0.05); table 1. In contrast, arachidonic (AA, p<0.005), AA:DHA ratio (p<0.005, fig 1) and total n-6 metabolites (p<0.05) were increased in the patients. Similarly, platelets from HbSS patients had low levels of eicosapentanoic acid (EPA, p<0.05), and raised AA (p<0.05) in choline phosphoglycerides (CPG); with reduced linoleic acid (LA, p<0.005) and DHA (p<0.05) in ethanolamine phosphoglycerides. Platelet CPG had lower DHA levels in HbSS individuals with complications of SCD compared to those who had no complications (p<0.05, fig.2). Reduced EPA and DHA relative to AA favours the production of aggregatory and pro-inflmmatory eicosanoids that activate leukocytes and platelets. This may lead to enhanced inflammation, leukocyte adhesion, platelet aggregation and vaso-occlusion in SCD.
Table 1: Fatty Acid Composition of MNC Total Phospholipids in HbSS Patients and HbAA Controls
Fatty Acids
HbSS Patients
HbAA Controls
24:0
0.71 [0.30]***
1.3 [0.4]
saturates ∑
38.2 [3.6]
39.1 [1.7]
16:1
0.69 [0.45]
0.56 [0.11]
18:1
14.4 [1.8]*
12.9 [1.9]
24:1
1.2 [0.3]
1.1 [0.4]
∑monoenes
16.2 [2.1]**
14.3 [1.4]
18:2n-6
6.1 [0.9]
7.0 [1.4]
18:3n-6
0.11 [0.04]*
0.23 [0.17]
20:2n-6
0.56 [0.18]**
0.83 [0.32]
20:3n-6 (DHGLA)
1.2 [0.2]*
1.4 [0.2]
20:4n-6
20.2 [1.7]***
18.1 [1.8]
22:4n-6
1.7 [0.4]
1.6 [0.4]
22:5n-6
0.3 [0.21]
0.24 [0.14]
n-6 metabolites ∑
24.1 [1.9]*
22.6 [1.7]
n-6 ∑
30.2 [2.0]
29.7 [2.2]
20:5n-3 (EPA)
0.43 [0.16]
0.61 [0.35]
22:6n-3 (DHA)
1.9 [0.4]**
2.5 [0.6]
∑n-3metabolites
4.3 [0.9]*
4.8 [0.4]
n-3 ∑
4.5 [0.9]*
5.0 [0.4]
DHGLA:AA ratio
0.06 [0.01]****
0.08 [0.01]
AA:EPA ratio
52.4 [20.9]
38.6 [18.4]
Values are Means [SD}. *p<0.05, **p<0.01, ***p<0.005, ****p<0.001
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