Participation of Mac-1, LFA-1 and VLA-4 integrins in the in vitro adhesion of sickle cell disease neutrophils to endothelial layers, and reversal of adhesion by simvastatin

摘要: Background Pharmacological approaches to inhibit increased leukocyte adhesive interactions in sickle cell disease may represent important strategies for the prevention of vaso-occlusion patients with this disorder. We investigated, vitro, adhesion molecules involved endothelial-sickle neutrophil and effect simvastatin on tumor necrosis factor-α-activated endothelial monolayers (human umbilical vein cells), chemotaxis.Design Methods Sickle steady state not hydroxyurea were included study. Endothelial cells treated, or not, factor-α used assays. Neutrophils treated submitted interleukin 8-stimulated chemotaxis assays.Results neutrophils showed greater than control neutrophils. Adhesion was mediated by Mac-1 under basal conditions LFA-1 integrins inflammatory conditions. In contrast, endothelium, both factor-α-stimulated conditions, also VLA-4. Under stimulated significantly reduced adhesion, reversed inhibition nitric oxide synthase. Furthermore, intercellular molecule-1 expression abrogated endothelium incubated simvastatin, statin treatment inhibited interleukin-8-stimulated migration neutrophils.Conclusions The Mac-1, and, interestingly, VLA-4 mediate leukocytes activated layers, vitro. Our data indicate that be able reduce activation consequent vitro model; future experiments clinical trials determine whether therapy could employed disease, beneficial effects vaso-occlusion.