Abstract
The pathologic features of sickle cell disease had been known in the past to be as a result of red cell abnormality leading to vascular occlusion, haemolysis and consequent anaemia. Recent knowledge has revealed numerous pathogenetic pathways involving leukocytes, platelets and the vascular endothelium. Complex interactions between the inflammatory cytokines and the membrane lipids in sickle cell present several pathogenetic processes affecting disease severity. The mechanisms of membrane fluidity, aggregation, adhesion and inflammation are strongly associated with membrane lipid constitution. The omega -3 fatty acids via incorporation into the lipid membrane have been found to play a central role in suppressing inflammation in several disease processes. Variations in disease severity have been shown to correspond with levels of fatty acid desaturases involved in the synthesis of these fatty acids. The genes coding for these substances can also be manipulated to achieve a favorable outcome and may provide several possible therapeutic and prophylactic access points This review aims at exploring these delicate interactions and proffering possible targets to ameliorate disease features. The information and referenced publications quoted in this review were obtained from the PubMed Central database, using the search keywords; inflammation, sickle cell, fatty acids and cytokines
Highlights
Sickle cell disease is an inherited disorder in which the mutant globin gene produces a less efficient haemoglobin molecule, causing depreciation in the resilience and flexibility of the red cells
This review aims to explore the inflammatory pathways involved in sickle cell disease (SCD) as well as the impact of the PUFAs, desaturases and their complex interactions with regards to the myriad of phenotypic presentation observed
These areas of the lipid membrane bi-layer, rich in cholesterol, sphingomyelin and saturated glycerol phospholipids are called rafts or micro-domains. Apart from their membrane function these rafts are known to influence intra-cellular signaling pathways, [8,18] affecting gene expression via their action on transcription factors [19,20]. These fatty acids are known to effect these actions by acting on transcription factors; nuclear factor κ, binding protein for the sterol regulatory element [21] and peroxisome proliferator activator receptor (PPAR) α and γ [22,23]
Summary
Sickle cell disease is an inherited disorder in which the mutant globin gene produces a less efficient haemoglobin molecule, causing depreciation in the resilience and flexibility of the red cells. These effects are known to include increased expression and binding of the cellular adhesion molecules to ligands on the vascular endothelium [1] a process similar to what is observed during inflammation [2]. Dietary omega-3 fatty acids are incorporated to a large extent into the cell membrane lipids and influence the composition of the rafts.
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