Human eosinophils are more toxic than neutrophils in antibody-independent killing

Abstract

Eosinophils (EOSs) are implicated in damaging host tissues in diseases such as asthma and eosinophilic gastroenteritis. In the present study, we assessed the cytotoxicity of human EOSs from peripheral blood of patients with eosinophilia and from peritoneal fluid of patients undergoing continuous peritoneal dialysis and compared them to normal neutrophils. Cytotoxicity was measured by the release of 51chromium from cultured tumor cells and chicken erythrocytes. Both EOSs and neutrophils were separated on discontinuous Percoll gradients with >95% purity. The granulocytes were activated by preincubation in an ice bath with phorbol myristate acetate and washed before incubation with the target cells. The EOSs lysed significantly more tumor cells (K562, Raji, and CEM lines) in an 18-hour assay than did neutrophils, and no significant difference was found between the peritoneal and blood EOSs. The EOSs were also much more efficient than neutrophils in lysing chicken erythrocytes when they were activated by granulocyte-macrophage colony-stimulating factor instead of phorbol myristate acetate. Cytolysis by EOSs is mediated by both oxidative and nonoxidative mechanisms, as indicated by experiments with cells from patients with chronic granulomatous disease. Thus, EOSs are much more cytotoxic than neutrophils and potentially much more damaging to patients with eosinophilia.