Enhanced neutrophil extravasation may be a contributing factor in the determination of neutropenia in patients with chronic idiopathic neutropenia of adults.

Abstract

To test the hypothesis that low numbers of circulating neutrophils may be due to enhanced neutrophil extravasation in patients with chronic idiopathic neutropenia of adults (CINA), serum levels of endothelial cell-derived soluble cell adhesion molecules (sE-selectin, sICAM and sVCAM) usually used as indicators of endothelial cell activation, serum levels of two potent endothelial cell activators (IL-1beta and TNF-alpha), and serum levels of the chemokine interleukin-8 (IL-8) which is one of the main chemoattractant substances for neutrophils at sites of inflammation, were measured in 84 CINA patients and 30 healthy volunteers using the respective micro-ELISA methods. We found that serum sE-selectin, sICAM, sVCAM, IL-1beta and TNF-alpha concentrations were all significantly increased in the group of patients compared to controls, and were correlated inversely with the number of circulating neutrophils. Serum levels of IL-8 were also markedly increased in the patients compared to controls, and they were correlated positively with the levels of serum sE-selectin, sICAM, sVCAM, IL-1beta and TNF-alpha, and inversely with the number of circulating neutrophils. No significant differences were noted between patients and normal controls in the proportions of neutrophils carrying the cell adhesion molecules CD11a/ CD18, CD15 and CD62L. These findings suggest strongly that CINA patients have activated endothelium to which circulating neutrophils may adhere by interacting with counter-structures found on their surface. Subsequent diapedesis and subendothelial migration may be facilitated by IL-8 and possibly other chemoattractant substances. We conclude that an enhanced neutrophil extravasation may be involved, at least in part, in the determination of neutropenia in CINA patients.