Eicosanoids in sickle cell disease: Potential relevance of neutrophil leukotriene B4 to disease pathophysiology

Abstract

Neutrophil activation with the release of intracellular granule contents has been observed in sickle cell disease (SCD). Because leukotriene B4 (LTB4), a 5-lipoxygenase metabolite of arachidonic acid in neutrophils, is a chemoattractant and enhances neutrophil adhesion to endothelium, we assessed plasma levels of this metabolite in controls (n = 9) and individuals with SCD, SS genotype, both in basal “steady state” (n = 37) and during episodes of vaso-occlusion (n = 10) and acute chest syndrome (n = 5). Thirteen patients with SCD, SC genotype, in steady state were also studied. Although no significant differences were noted between the control (136 ± 32 fmol/mL) and SC genotype (177 ± 83 fmol/mL, P >.15), LTB4 levels were markedly increased in patients with SS genotype in basal steady state (207 ± 64 fmol/mL, P <.003) compared with those in controls. Values were further increased during vaso-occlusion (264 ± 94 fmol/mL) and acute chest syndrome (363 ± 124 fmol/mL). These levels were significantly different from measurements taken during steady state (P <.04 and P <.0001, respectively). No correlation was noted between LTB4 level and total white cell or neutrophil count. Additionally, the significant correlation noted in SCD between increased levels of plasma LTB4 and soluble L-selectin (P <.03) reflects neutrophil activation. We also observed an effect of LTB4 on red cell-endothelial adhesion at concentrations that appear clinically relevant (1-10 pmol/mL) with concomitant up-regulation of mRNA for the endothelial vitronectin receptor. These properties of LTB4 are relevant to disease pathophysiology, providing further evidence of the contribution of the neutrophil to the proinflammatory and proadhesive phenotype in SCD. (J Lab Clin Med 2002;139:80-9)