Correlation between CCL26 production by human bronchial epithelial cells and airway eosinophils: Involvement in patients with severe eosinophilic asthma.
BACKGROUND
High pulmonary eosinophil counts are associated with asthma symptoms and severity. Bronchial epithelial cells (BECs) produce CC chemokines, notably CCL26 (eotaxin-3), which recruits and activates eosinophils from asthmatic patients. This suggests that CCL26 production by BECs might be involved in persistent eosinophilia in patients with severe asthma despite treatment with high corticosteroid doses.


OBJECTIVE
We sought to determine whether CCL26 levels correlate with eosinophilia and asthma severity.


METHODS
Human CC chemokine expression was assessed by means of quantitative PCR or a quantitative PCR array in vehicle- or IL-13-treated BECs. CCL26 was quantitated by means of ELISA. Immunohistochemistry analyses of CCL26 and major basic protein were done on bronchial biopsy specimens.


RESULTS
IL-13 selectively induced CCL26 expression by BECs. This increase was time-dependent and more prominent in BECs from patients with severe eosinophilic asthma. CCL26 levels measured in supernatants of IL-13-stimulated BECs also increased with asthma severity as follows: patients with severe eosinophilic asthma > patients with mild asthma ≈ healthy subjects. Immunohistochemistry analyses of bronchial biopsy specimens confirmed increased levels of CCL26 in the epithelium of patients with mild and those with severe eosinophilic asthma. Tissue eosinophil counts did not correlate with CCL26 staining. However, sputum CCL26 levels significantly correlated with sputum eosinophil counts (P < .0001), suggesting that CCL26 participates in the movement of eosinophils from the tissues to the airway lumen.


CONCLUSIONS
These results show a relation between CCL26 production by IL-13-stimulated BECs, sputum eosinophil counts, and asthma severity. They also suggest a role for CCL26 in the sustained inflammation observed in patients with severe eosinophilic asthma and reveal CCL26 as a potential target for treating patients with eosinophilic asthma that are refractory to classic therapies.
Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Faculté de médecine, Université Laval, Quebec City, Quebec, Canada.
Marie-Chantal
MC
Larose
Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Faculté de médecine, Université Laval, Quebec City, Quebec, Canada.
Jamila
J
Chakir
Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Faculté de médecine, Université Laval, Quebec City, Quebec, Canada.
Anne-Sophie
AS
Archambault
Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Faculté de médecine, Université Laval, Quebec City, Quebec, Canada.
Philippe
P
Joubert
Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Faculté de médecine, Université Laval, Quebec City, Quebec, Canada.
Véronique
V
Provost
Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Faculté de médecine, Université Laval, Quebec City, Quebec, Canada.
Michel
M
Laviolette
Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Faculté de médecine, Université Laval, Quebec City, Quebec, Canada. Electronic address: Nicolas.Flamand@criucpq.ulaval.ca.
Nicolas
N
Flamand
D000328:Adult; D001249:Asthma / Q000276:immunology*; D001980:Bronchi / Q000473:pathology*; D002478:Cells, Cultured; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000378:metabolism*; D018450:Disease Progression; D047093:Eosinophil Major Basic Protein / Q000378:metabolism; D004802:Eosinophilia / Q000276:immunology*; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018793:Interleukin-13 / Q000276:immunology; D008297:Male
C120429:CCL26 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D018793:Interleukin-13; D047093:Eosinophil Major Basic Protein
Asthma; CCL26; IL-13; bronchial epithelial cells; bronchial mucosa; chemokine; eotaxin; inflammation; severe asthma