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Am J Physiol Lung Cell Mol Physiol 290: L588-L596, 2006. First published November 4, 2005; doi:10.1152/ajplung.00013.2005
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Adherence of airway neutrophils and inflammatory response are increased in CF airway epithelial cell-neutrophil interactions

Olivier Tabary,1,* Harriet Corvol,1,2,* Emilie Boncoeur,1 Katarina Chadelat,1,2 Catherine Fitting,3 Jean Marc Cavaillon,3 Annick Clément,1,2 and Jacky Jacquot1

1Institut National de la Santé et de la Recherche Médicale, U719, F-75012 Paris, France; Université Pierre et Marie Curie Paris VI; 2Service de Pédiatrie-Pneumologie, Hôpital Armand Trousseau; and 3Unité Cytokines & Inflammation, Institut Pasteur, Paris, France

Submitted 10 January 2005 ; accepted in final form 23 October 2005

Persistent presence of PMN in airways is the hallmark of CF. Our aim was to assess PMN adherence, percentage of apoptotic airway PMN (aPMN), and IL-6 and IL-8 production when aPMN are in contact with airway epithelial cells. Before coculture, freshly isolated CF aPMN have greater spontaneous and TNF-{alpha}-induced apoptosis compared with blood PMN from the same CF patients and from aPMN of non-CF patients. We then examined cocultures of PMN isolated from CF and non-CF airways with bronchial epithelial cells bearing mutated cftr compared with cftr-corrected bronchial epithelial cells. After 18-h coculture, the number of CF aPMN adhered on cftr-deficient bronchial epithelial cells was 2.3-fold higher compared with the coculture of non-CF aPMN adhered on cftr-corrected bronchial epithelial cells. The percentage of CF apoptotic aPMN (9.5 ± 0.2%) adhered on cftr-deficient bronchial epithelial cells was similar to the percentage of non-CF apoptotic aPMN adhered on cftr-corrected bronchial epithelial cells (10.3 ± 0.7%). IL-6 and IL-8 levels were enhanced 6.5- and 2.9-fold, respectively, in coculture of CF aPMN adhered on cftr-deficient bronchial epithelial cells compared with coculture of non-CF aPMN adhered on cftr-corrected bronchial epithelial cells. Moreover, blocking surface adhesion molecules ICAM-1, VCAM-1, and E-selectin on cftr-deficient bronchial epithelial cells with specific MAbs inhibited the adherence of CF aPMN by 64, 51, and 50%, respectively. Our data suggest that in CF patients a high number of nonapoptotic PMN adhered on airway epithelium associated with elevated IL-6 and IL-8 levels may contribute to sustained and exaggerated inflammatory response in CF airways.

cystic fibrosis; epithelial cell; airway neutrophil; adherence; apoptosis; interleukin-6; interleukin-8


Address for reprint requests and other correspondence: J. Jacquot, Inserm U719, Hôpital St-Antoine, Bâtiment Kourilsky, 184, rue du Fg St-Antoine, F-75571 Paris, France (e-mail: jacky.jacquot{at}st-antoine.inserm.fr)




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