Inflammatory potential of neutrophils detected in sickle cell disease

An early event in the inflammatory response is neutrophil recruitment to endothelium in response to chemotactic stimulation, which in turn activates CD18-integrin, which anchors neutrophils to the vessel wall under the shear force of blood flow. Activated neutrophils circulating in sickle cell disease (SCD) patients may significantly contribute to vascular occlusions (VOC) as neutrophils adherent to inflamed endothelium recruit sickle red blood cells inducing VOC. To elucidate the mechanisms by which neutrophils may participate in VOC in SCD, CD18-integrin expression and function in fresh blood samples of non-crisis patients were measured by flow cytometry. CD11b/CD18 membrane expression was similar to70% higher on unstimulated SCD neutrophils than controls, which correlated with a 1-fold higher rate of adhesion to ligand. Unstimulated SCD neutrophils expressed similar to30,000 active CD18 per cell, while controls expressed similar to6,000. Stimulation with a low concentration of IL-8 (0.1 nM) upregulated 100% more active CD18 and induced 60% more adhesion of SCD than control neutrophils. These data demonstrate that neutrophils from SCID patients constitutively express active CD18 in blood and respond with enhanced sensitivity to chemokine activation of adhesion, thus increasing their propensity for exuberant adhesion. (C) 2004 Wiley-Liss, Inc.