Adhesion molecules and hydroxyurea in the pathophysiology of sickle cell disease

Omega 3 (n−3) fatty acids down-regulate nuclear factor-kappa B (NF-κB) gene and blood cell adhesion molecule expression in patients with homozygous sickle cell disease

“…Knowing that NF-κB pathway mediates oxidative stress response [60], the observed reduction in NF-κB gene expression could be a reflection to the observed improvements in the patients' oxidative stress status after supplementation with n−3 fatty acids [19]. The results of the present study might also suggest pathways other than NF-κB gene involved in hydroxyurea well-documented anti-adhesive effects [9].…”

“…Indeed, it has been demonstrated that inflammation and increased leukocyte-erythrocyte-endothelial interactions are the major potential initiating mechanisms of recurrent occlusion of blood vessels [5,6]. In addition, the therapeutic effect of hydroxyurea, the common treatment for SCD, and some emerging experimental treatments is chiefly attributed to their anti-inflammatory and anti-adhesive properties [7][8][9][10].…”

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

“…Moreover, there is evidence that white blood cells of sickle cell patients, which seem to have a higher propensity to adhere to vascular endothelium, play a critical role vasoocclusion (Canalli et al, 2008;Frenette, 2002Frenette, , 2004. Leukocytes adhesion to vascular endothelium is mediated by the interaction of leukocyte adhesion molecules L-selectin (CD62L), αMβ2 integrine (CD11b/CD18) and LFA-1 (CD11A/CD18) with endothelial adhesion molecules including, intercellular adhesion molecule-1, vascular adhesion molecule-1 (VCAM-1), E-selectin, and P-selectin (Johnson and Telen, 2008;Okpala, 2002;Turhan et al, 2002). The fact that leukocytes are far larger, stiffer, and stickier than red cells, they are more effective in slowing microvascular blood flow, and ultimately, the initiation and propagation of vasoocclusion (Chiang and Frenette, 2005;Hebbel et al, 2009).…”

“…However, clinical improvements do occur prior to a significant rise in levels of HbF (Charache et al, 1996) suggesting that HU may modulate the pathophysiology of the disease through other additional mechanisms. Indeed, emerging evidence reveals that the mechanisms of action of HU involve a reduction of leukocytes, reticulocyte and platelet counts (Ballas et al, 1999), myeloperoxidase activity, blood cell adhesion (Johnson and Telen, 2008), the externalization of the proaggregatory aminophospholipid, serine (Covas et al, 2004), and an increased production of NO (Nahavandi et al, 2002).…”

Genética das doenças hematológicas: as hemoglobinopatias hereditárias

“…68 There is also evidence that HU affects hydration of red blood cells, adhesion to the endothelium and NO production. [68][69][70][71][72][73][74] Possibly also as a result of the suppressor effect, patients who take HU have lower numbers of circulating reticulocytes and less dense cells. 68,70 The safety and efficacy of HU in the majority of adult patients are well established.…”