Cystic fibrosis transmembrane conductance regulator does not affect neutrophil migration across cystic fibrosis airway epithelial monolayers

Article Article scientifique Article Cystic fibrosis transmembrane conductance regulator does not affect neutrophil migration across cystic fibrosis airway epithelial monolayers eng 2000 author Pizurki Lara Johanna 23014 author Morris Michael Andréw 24090 author Chanson Marc 0000-0001-8104-2090 32865 author Solomon Melete 27876 author Pavirani Andréa author Bouchardy Isabelle 46083 author Suter Susanne 22780 1407-1416 10.1016/S0002-9440(10)65009-2 10751364 0002-9440 Recent studies have shown that airway inflammation dominated by neutrophils, ie, polymorphonuclear cells (PMN) was observed in infants and children with cystic fibrosis (CF) even in the absence of detectable infection. To assess whether there is a CF-related anomaly of PMN migration across airway epithelial cells, we developed an in vitro model of chemotactic migration across tight and polarized CF(15) cells, a CF human nasal epithelial cell line, seeded on porous filters. To compare PMN migration across a pair of CF and control monolayers in the physiological direction, inverted CF(15) cells were infected with increasing concentrations of recombinant adenoviruses containing either the normal cystic fibrosis transmembrane conductance regulator (CFTR) cDNA, the DeltaF508 CFTR cDNA, or the beta-galactosidase gene. The number of PMN migrating in response to N-formyl-Met-Leu-Phe across inverted CF(15) monolayers expressing beta-galactosidase was similar to that seen across CF(15) monolayers rescued with CFTR, whatever the proportion of cells expressing the transgene. Moreover, PMN migration across monolayers expressing various amounts of mutated CFTR was not different from that observed across matched counterparts expressing normal CFTR. Finally, PMN migration in response to adherent or Pseudomonas aeruginosa was equivalent across CF and corrected monolayers. The possibility that mutated CFTR may exert indirect effects on PMN recruitment, via an abnormal production of the chemotactic cytokine interleukin-8, was also explored. Apical and basolateral production of interleukin-8 by polarized CF cells expressing mutated CFTR was not different from that observed with rescued cells, either in baseline or stimulated conditions. CF(15) cells displayed a CF phenotype that could be corrected by CFTR-containing adenoviruses, because two known CF defects, Cl(-) secretion and increased P. aeruginosa adherence, were normalized after infection with those viruses. Thus, we conclude that the presence of a mutated CFTR does not per se lead to an exaggerated inflammatory response of CF surface epithelial cells in the absence or presence of a bacterial infection. Adenoviridae/genetics Bacterial Adhesion/physiology Cell Movement/drug effects Cell Polarity Cells, Cultured Cystic Fibrosis/pathology/physiopathology Cystic Fibrosis Transmembrane Conductance Regulator/genetics/pharmacology Gene Expression Humans Interleukin-8/metabolism Mutation/physiology Nasal Mucosa/pathology/physiopathology Neutrophils/drug effects/microbiology/physiology Pseudomonas aeruginosa/physiology Reference Values Transgenes/genetics Dewey 576.5 Dewey 618 135 Département de médecine génétique et développement 21D 58 Département de pédiatrie, gynécologie et obstétrique 223 false 180 Mucoviscidose et jonctions GAP 229 The American journal of pathology 156 4 595d7ffe-70ad-45d4-bb9e-ca625a5997a9 Article (Published version) Restricted Pizurki-2000-Cystic fibrosis tran.pdf 328844 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique

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Cystic fibrosis transmembrane conductance regulator does not affect neutrophil migration across cystic fibrosis airway epithelial monolayers	The American journal of pathology			2000	661	0

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Solomon, Melete