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.

Dietary supplementation with docosahexanoic acid (DHA) increases red blood cell membrane flexibility in mice with sickle cell disease

“…As dietary supplements, omega-3 fatty acids are beneficial in many cardiovascular diseases [27;37;38;41;49]. In addition, Ren et al [56–58] demonstrated that humans with SCD have decreased omega-3 fatty acids and increased arachidonic acid (an omega-6 fatty acid) in the RBC membrane. To date, trials in humans with SCD have indicated that dietary supplementation with omega-3 fatty acids may reduce severe anemia, vaso-occlusive pain episodes, white blood cell count, and prothrombotic activity [18;52;64].…”

Correlates of Steady State Lipid Profile and Anthropometric Parameters in Adult Sickle Cell Anaemia Patients in South-West Nigeria

“…Studies done on the effect of alternative dietary lipid therapy showed that supplementation with N-3 fatty acid exerted a positive benefit on blood viscosity, platelet count, fibrinogen and fatty acid composition of red blood cells and platelets. [11][12][13] Anthropometric measurements can easily reflect changes in the lipid deposition in the human body. Study shows that total cholesterol (TC), low density lipoprotein (LDL) and triglyceride (TG) increase with age and body mass index BMI 14 .…”

Blood Cell Membrane Omega-3 ( n -3) Fatty Acid Abnormality and Supplementation in Patients with Sickle Cell Anemia

“…This abnormality, which was evident in the inner and outer leaflets of the lipid bilayer, was manifested primarily by an increase in arachidonic acid (AA, 20:4n-6) and a concomitant decrease in the omega-3 fatty acids, eicosapentaenoic (EPA, 20:5n-3), and docosahexaenoic (DHA, 22:6n-3). Perhaps, more surprisingly, the mononuclear cells and platelets of the patients, although not affect directly by the genetic defect, had the same fatty acid abnormality as the red blood cells (Figure 27.1).Therefore, it appears that the high omega-6 and low omega-3 fatty acids of blood cells is a peculiar biochemical feature of the disease and unlikely to be a reflection of nutritional intake (Connor et al, 1997;Daak et al, 2011;Manodori et al, 2000;Ren et al, 2005bRen et al, , 2006.…”

“…Moreover, there is evidence that platelets and mononuclear cells of patients with the disease have defective phospholipid fatty acid composition (Ren et al, 2005b). These abnormalities are thought to play a significant role in the pathophysiology and clinical severity of the disease (Hebbel, 1991).…”

“…We have investigated fatty acid composition of (i) red blood cells of Nigerian HbSS patients and matched health controls, (ii) red blood cells, platelets and mononuclear cells of British HbSS patients and healthy controls (Ren et al, 2005a(Ren et al, , 2005b, and (iii) red blood cells of Sudanese HbSS patients and controls (Daak et al, 2011). The red cells of the patients from the three countries with contrasting environmental and nutritional background had abnormal fatty acid composition.…”