Adherence of airway neutrophils and inflammatory response are increased in CF airway epithelial cell-neutrophil interactions.
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.
Tabary
Olivier
O
Inserm U719, Hôpital St-Antoine, Bâtiment Kourilsky, 184, rue du Fg St-Antoine, F-75571 Paris, France.
Corvol
Harriet
H
Boncoeur
Emilie
E
Chadelat
Katarina
K
Fitting
Catherine
C
Cavaillon
Jean Marc
JM
Clément
Annick
A
Jacquot
Jacky
J
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D016022:Case-Control Studies; D002448:Cell Adhesion; D002450:Cell Communication; D002675:Child, Preschool; D018920:Coculture Techniques; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology*; D019040:E-Selectin / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D008297:Male; D009504:Neutrophils / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; C505032:CFTR protein, human; D019040:E-Selectin; D015850:Interleukin-6; D016209:Interleukin-8; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019005:Cystic Fibrosis Transmembrane Conductance Regulator