Inhibition of CFU-NM and CFU-EOS by mature granulocytes.

Approximately half of the colony-forming units-culture (CFU-C) from normal peripheral blood are eosinophilic. The purpose of our study was to determine: (1) whether progenitor cells committed to eosinophil or neutrophil maturation would be differentially affected by feedback inhibition, and (2) whether mature eosinophils added to the feeder layers of the culture would inhibit the proliferation of CFU-C in a manner similar to that described for neutrophils. Concentrated eosinophils and neutrophils, obtained by separation on a metrizamide gradient, were added to feeder layers containing either 10(6) autologous whole mononuclear cells (WMNC) or 0.1 ml of leukocyte conditioned media (LCM). The average number of colonies was 123/10(6) nonadherent cells (NAC) cultured. When neutrophils or eosinophils were added to the WMNC feeder layer, the percent inhibition of growth was 40.2% +/- 1.6% (mean +/- SEM) and 42.3% +/- 5.4%, respectively, but the ratio of neutrophil to eosinophil colonies remained constant. No effect was seen when neutrophils or eosinophils were added to an LCM feeder layer. Thus, it appears that the differential control of neutrophil versus eosinophil production in vitro is not regulated through feedback inhibition by mature granulocytes. In addition, these studies suggest that eosinophils, as well as neutrophils, cause inhibition of CFU-C growth when intact cells are the source of colony-stimulating factor (CSF).

Superoxide production by eosinophils: activation by histamine.

Both guinea pig peritoneal exudate and human peripheral blood eosinophils produce large amounts of superoxide anion when stimulated by preopsonized zymosan or phorbol myristate acetate (PMA). Superoxide production is also activated by histamine but not the histamine metabolite, imidazole acetic acid. Supernatants from degranulated rat mast cells stimulate superoxide production. In studies of both human and guinea pig eosinophils, the H1-antagonist, chlorpheniramine (10-3 M and 10-4 M), preopsonized zymosan histamine) production of superoxide anion but the H2-antagonist, cimetidine, only modestly inhibited superoxide anion production (zymosan, PMA), These studies provide direct evidence for the influence of histamine on the oxidative metabolism of eosinophils. These results are consistent with the hypothesis that histamine interacts with eosinophils predominantly via an H1 receptor site. Furthermore, they suggest that eosinophils may participate in immediate hypersensitivity reactions by the release of superoxide anion in response to stimulation by histamine.

Metabolic heterogeneity of eosinophils from normal and hypereosinophilic patients.

Eosinophils, which may be associated with allergic, parasitic, or neoplastic disease, have a potent oxidative burst that may be activated by particulate or soluble stimuli. Eosinophils from normal persons and patients with hypereosinophilia were compared with respect to their ability to produce the active oxygen product, superoxide anion. Normal eosinophils produced large amounts of superoxide anion under resting conditions (0.53 +/- 0.15 nmoles cyto-c/10(5) eos/hr) and when stimulated by preopsonized zymosan (0.85 +/0 1.10 nmoles cyto-c/10(5) eos/hr) or phorbol myristate acetate (PMA) (2.38 +/- 0.46 nmoles cyto-c/10(5) eos/hr). Considerable variation was observed in superoxide production by eosinophils from patients with hypereosinophilia. Eosinophils from a group of four patients with hypereosinophilia associated with neoplastic disease produced less superoxide anion than normal eosinophils when stimulated by preopsonized zymosan or PMA (p less than or equal to 0.05). Eosinophils from a group of 5 patients with other causes of hypereosinophilia produced more superoxide anion than normal eosinophils when stimulated by PMA (p less than or equal to 0.01). These studies demonstrate metabolic heterogeneity of eosinophils from patients with hypereosinophilia, and further emphasize that normal eosinophils and eosinophils from hypereosinophilic patients are not functionally equivalent.