Human eosinophils are activated by necrotic epithelial cells

Abstract

Rationale Eosinophils are involved in a variety of allergic and other inflammatory conditions such as asthma, pulmonary fibrosis, lung cancer, food allergy, inflammatory bowels disease, and are often associated with tissue destruction. We have examined if eosinophils migrate, degranulate and release growth factors upon stimulation with necrotic epithelial cells. Methods Human eosinophils were isolated from blood donors by negative depletion with anti-CD16 beads. Epithelial cell lines from the tissues where eosinophil preferentially accumulate (gastrointestinal, respiratory and genitourinary tract) were damaged by freeze-pressing. Eosinophil migration, release of eosinophil peroxidase, fibroblast growth factor-2 (FGF-2) and transforming growth factor-b1 was assessed by microwell migration system, enzyme assay and sandwich ELISA respectively. Results Damaged gastrointestinal cells attracted significantly more eosinophils compared with the undamaged gastrointestinal cells. Necrotic genitourinary cells, on the other hand, stimulated eosinophils to degranulate to a significantly higher extent compared to viable genitourinary cells. Eosinophils stimulated by freeze-pressed gastrointestinal and genitourinary cells seemed to released large amounts of FGF-2. Endotoxin contamination of the epithelial cells is not likely to have contributed to the observed effects, since lipopolysaccharide in the absence of human serum was unable to elicit eosinophil activation. Conclusion Eosinophils recognize and are activated by damaged epithelial cells, which may be relevant to understanding their function in the variety of diseases they are involved in.