Eosinophil degranulation in the presence of bronchial epithelial cells. Effect of cytokines and role of adhesion.
It has been suggested that eosinophils (Eos) are responsible for damage to bronchial epithelial cells by releasing toxic eosinophil granule proteins in bronchial asthma. We examined eosinophil cationic protein (ECP) release from human Eos cultured in the presence of human bronchial epithelial cell line BEAS-2B (Ep). ECP release was potentiated only when both Eos and Ep were activated by IL-5 and TNF, respectively, while it was not potentiated when either Eos or Ep were activated. ECP release from Eos activated by IL-5 was also enhanced when Ep was stimulated by IFN-gamma. Paraformaldehyde fixation of Ep had no effect on ECP enhancement, excluding the possibility that soluble factors from Ep contribute to ECP potentiation. Coculture of Eos and Ep with cytokine treatment resulted in the enhancement of eosinophil adhesion and ECP release, and eosinophil adhesion preceded ECP release in the kinetic study. The enhancement of ECP release was partially inhibited by anti-CD18 mAb, which caused partial and comparable inhibition on the potentiation of eosinophil adhesion. These results suggest that the activation of Ep may profoundly affect the ability of cocultured Eos to release ECP and that CD18-dependent adhesion of Eos to Ep may be considered as one of the mechanisms of ECP enhancement.
Takafuji
S
S
Department of Medicine and Physical Therapy, Faculty of Medicine, University of Tokyo, Japan.
Ohtoshi
T
T
Takizawa
H
H
Tadokoro
K
K
Ito
K
K
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001798:Blood Proteins / Q000187:drug effects / Q000378:metabolism; D001980:Bronchi / Q000166:cytology / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology / Q000502:physiology*; D015550:Cell Degranulation / Q000276:immunology; D018920:Coculture Techniques; D016207:Cytokines / Q000494:pharmacology*; D003594:Cytoplasmic Granules / Q000187:drug effects* / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D004357:Drug Synergism; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D004847:Epithelial Cells; D004848:Epithelium / Q000276:immunology; D006801:Humans; D015848:Interleukin-5 / Q000494:pharmacology; D012260:Ribonucleases; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D001798:Blood Proteins; D016207:Cytokines; D047091:Eosinophil Granule Proteins; D015848:Interleukin-5; D014409:Tumor Necrosis Factor-alpha; D012260:Ribonucleases