ENHANCED NEUTROPHIL EXTRAVASATION MAY BE A CONTRIBUTING FACTOR IN THEDETERMINATION OF NEUTROPENIA IN PATIENTS WITH CHRONIC IDIOPATHIC NEUTROPENIA OF ADULTS

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 c ell-derived soluble cell adhesion molecules (sE-selectin, sICAM and sV CAM) usually used as indicators of endothelial cell activation, serum levels of two potent endothelial cell activators (IL-1 beta and TNF-al pha), 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 volunt eers using the respective micro-ELISA methods. We found that serum sE- selectin, sICAM, sVCAM, IL-1 beta and TNF-a concentrations were all si gnificantly increased in the group of patients compared to controls, a nd were correlated inversely with the number of circulating neutrophil s. Serum levels of IL-8 were also markedly increased in the patients c ompared to controls, and they were correlated positively with the leve ls of serum sE-selectin, sICAM, sVCAM, IL-1 beta and TNF-alpha, and in versely with the number of circulating neutrophils. No significant dif ferences were noted between patients and normal controls in the propor tions of neutrophils carrying the cell adhesion molecules CD11a/CD18, CD15 and CD62L. These findings suggest strongly that CINA patients hav e activated endothelium to which circulating neutrophils may adhere by interacting with counter-structures found on their surface. Subsequen t diapedesis and subendothelial migration may be facilitated by IL-8 a nd possibly other chemoattractant substances. We conclude that an enha nced neutrophil extravasation may be involved, at least in part, in th e determination of neutropenia in CINA patients.