Blood mononuclear cells and platelets have abnormal fatty acid composition in homozygous sickle cell disease

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

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 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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