Comparison of the role of nasal polyp and normal nasal mucosal epithelial cells on in vitro eosinophil survival. Mediation by GM-CSF and inhibition by dexamethasone.
Eosinophilic infiltration of the respiratory mucosa is considered an inflammatory hallmark of allergic rhinitis, bronchial asthma and nasal polyposis. However, the mechanisms involved in this infiltration have not yet been totally elucidated. The objective of this study was to investigate and compare the influence of epithelial cell secretions from both nasal polyps (NP) and normal nasal mucosa (NM) on in vitro eosinophil survival. Epithelial cells were identified by microscopy and immunohistochemistry, cultured to confluence, and human epithelial cell conditioned media (HECM) was generated from cultures. Eosinophils were isolated at high viability and purity (> 90%) from peripheral blood and incubated with HECM. HECM from both NM and NP increased eosinophil survival in a dose-dependent manner, this effect being maximal at a concentration of 25% for NM (73.4% +/- 5.5%, n = 26, P < 0.001) and of 10% for NP (74.5% +/- 8.4%, n = 18, P < 0.001). Incubation of monoclonal antibody to human GM-CSF with HECM, neutralized the induction of eosinophil survival by HECM from both NM and NP. HECM from NP contained higher concentrations of GM-CSF (111 +/- 25.4 pg/ml, n = 17) than HECM from NM (97.1 +/- 15.2 pg/ml, n = 8), without reaching statistical significance. Pre-incubation of dexamethasone with eosinophils also blocked HECM-induced eosinophil survival from both NM (10(-8)-10(-5) M; IC50 = 9.5 nM) and NP (10(-7)-10(-5) M; IC50 = 83 nM). These results suggest that: firstly eosinophil infiltration into the respiratory mucosa during allergic reaction and nasal polyposis may be modulated at least in part by GM-CSF from epithelial cells; and secondly epithelial cells from NP might have a more potent effect on inducing eosinophil infiltration of the respiratory mucosa than epithelial cells from NM. Finally, we may consider this as a reliable in vitro model to compare the role of epithelial cells from inflammatory (NP) and non-inflammatory (NM) tissue in respiratory inflammation.
Serveis de Pneumologia i Hematologia, Hospital Clinic, Barcelona, Catalonia, Spain.
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Xaubet
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Mullol
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López
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Roca-Ferrer
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Rozman
T
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Carrión
J M
JM
Fabra
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Picado
D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D017077:Culture Media, Conditioned; D003907:Dexamethasone / Q000494:pharmacology; D004804:Eosinophils / Q000166:cytology* / Q000187:drug effects; D004847:Epithelial Cells; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D009297:Nasal Mucosa / Q000166:cytology*; D009298:Nasal Polyps / Q000473:pathology*
D017077:Culture Media, Conditioned; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor