Superoxide Generation by Hypodense Eosinophils from Patients with Asthma

Abstract

Low density, or hypodense eosinophils (HE) are found in increased numbers in asthma. Since HE have been reported to have increased inflammatory potential and correlate with the severity of airway obstruction, it has been suggested that this subpopulation of eosinophils may contribute to the asthma process. However, investigations to define the function of HE in asthma have been limited. In this study, pure populations of both HE and normal dense eosinophils were isolated from the peripheral blood of seven patients with asthma, and functional activity of these cells was determined by measuring superoxide (O2-) generation to several activators. Compared to normal dense eosinophils, HE generated significantly more O2- when activated with the chemotactic peptide FMLP or opsonized zymosan; however, these differences were small. In contrast, no difference was observed in O2- production between normal- and low-density eosinophils from asthma patients when stimulated by phorbol myristate acetate (PMA) or the calcium ionophore A23187. Furthermore, both eosinophil populations, and corresponding neutrophil isolates, from asthma patients generated significantly more O2- than control granulocytes when activated by PMA. When stimulated by calcium ionophore, all three eosinophil populations released equivalent amounts of O2-, which were, however, higher than from both neutrophil suspensions. Compared to increased activity found in some other hypereosinophilic conditions, blood HE in asthma do not necessarily have enhanced function. This suggests that eosinophil heterogeneity extends not only to cell density but is also reflected in cell function and that these cell variations are dependent on many factors, including the function assessed, source of cells (normal versus patients with some diseases), and stimulus used.