Protease-dependent activation of nasal polyp epithelial cells by airborne fungi leads to migration of eosinophils and neutrophils.
CONCLUSIONS
Proteases in fungi interact with nasal epithelial cells and enhance the production of inflammatory cytokines in vitro. These cytokines induced the migration of eosinophils and neutrophils. Protease-activated receptors (PARs) might also play a role in the process of epithelial cell activation.


OBJECTIVE
The nasal epithelium is the first barrier encountered by airborne allergens and an active participant in airway inflammation. Fungi have been increasingly recognized as important pathogens in sinusitis and consist of several allergenic proteins.


METHODS
Nasal polyp epithelial cells were obtained from patients and stimulated with Alternaria, Aspergillus, and Cladosporium. Interleukin-8 (IL-8), granulocyte-macrophage colony stimulating factor (GM-CSF), and regulated on activation normal T expressed and secreted (RANTES) were measured to determine the activation of epithelial cells. Reverse transcriptase-polymerase chain reaction test (RT-PCR) for PAR mRNA expression in nasal epithelial cells was performed. Eosinophil and neutrophil migration was induced with nasal polyp epithelial cells conditioned media (HPECM).


RESULTS
Fungi enhanced the production of chemical mediators from nasal epithelial cells. When nasal epithelial cells were activated with fungi, PAR2 and PAR3 mRNAs were more strongly expressed than in nonactivated cells. Eosinophil migration was induced by RANTES and eotaxin, and neutrophil migration was induced by IL-8 in HPECM.
Shin
Seung-Heon
SH
Department of Otolaryngology, School of Medicine, Catholic University of Daegu, Daegu, Korea. hsseung@cu.ac.kr
Lee
Young-Ho
YH
Jeon
Chang-Ho
CH
D000485:Allergens; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism; D017077:Culture Media, Conditioned; D004804:Eosinophils / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology*; D005658:Fungi / Q000201:enzymology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D009298:Nasal Polyps / Q000378:metabolism / Q000503:physiopathology*; D009504:Neutrophils / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D044462:Receptors, Proteinase-Activated / Q000378:metabolism / Q000502:physiology*
D000485:Allergens; C515456:CCL11 protein, human; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D019742:Chemokines, CC; D017077:Culture Media, Conditioned; D016209:Interleukin-8; D012333:RNA, Messenger; D044462:Receptors, Proteinase-Activated; D016178:Granulocyte-Macrophage Colony-Stimulating Factor