The Effects of Activated Nasal Polyp Epithelial Cells by Fungi on Activation and Migration of Neutrophils

Kim, Jeong Kyu; Shin, Seung Heon; Kim, Yong Dae

Abstract

BACKGROUND AND OBJECTIVES
Sinusitis is one of the most common chronic disease in otolaryngology but it's pathogenesis is not well understood. Fungi are known to induce the production of chemical mediators from respiratory epithelial cells and have been increasingly recognized as important pathogens in sinusitis. As neutrophils and fungi are commonly present in the rhinosinusitis tissues and nasal secretions, we conducted this study to figure out the relationship between fungi and neutrophils in the pathogenesis of rhinosinusitis. SUBJECTS AND METHOD: To make human nasal polyp epithelial cell conditioned media (HPECM), nasal polyp epithelial cells were stimulated with 25 microgram/ml of Aspergillus, Aspergillus, 50 microgram/ml of Alternaria and Bipolaris, respectively. Peripheral blood neutrophils were incubated with HPECM to activate and induce the migration of neutrophils. Superoxide production and myeloperoxidase (MPO) were measured as a marker of neutrophils activation. Neutrophil activation was inhibited with anti-IL-8, anti-GM-CSF, and anti-RANTES antibodies, and protease inhibitors (E-64, Pefabloc, Aprotinine). Neutrophil migration were inhibited with anti-IL-8, anti-GM-CSF, anti-RANTES antibodies. RESULTS: HPECM induced the activation of neutrophils. Although the superoxide productions were not strongly enhanced, neutrophils produced a large amount of MPO (61.69+/-47.54 ng/ml by Alternaria, 77.58+/-34.26 ng/ml by Aspergillus, 59.20+/-27.65 ng/ml by Bipolaris). Anti-chemical mediator antibodies and protease inhibitors didn't inhibit the activation of neutrophils. Neutrophil migrations were increased by HPECM and anti-IL8 antibody inhibited the migration of neutrophils (60.5% of Alternaria, 65.5% of Aspergillus, 87.2% of Bipolaris). CONCLUSIONS: Fungi induced the production of chemical mediators from the nasal epithelial cells. HPECM which contains the chemical mediator activated the neutrophils and enhanced their migration. Although the activating factors of neut-rophils couldn't be determined, IL-8 seems to play an important role in the migration of neutrophils.