PSEUDOMONAS-AERUGINOSA LIPOPOLYSACCHARIDE INDUCES CF-LIKE ALTERATION OF PROTEIN SECRETION BY HUMAN TRACHEAL GLAND-CELLS

Human tracheal gland (HTG) serous cells are now believed to play a maj or role in the physiopathology of cystic fibrosis. Because of the pers istent inflammation and the specific infection by Pseudomonas aerugino sa in the lung, we looked for the action of the lipopolysaccharide (LP S) of this bacteria on human tracheal gland cells in culture by studyi ng the secretion of the secretory leukocyte proteinase inhibitor (SLPI ) which is a specific serous secretory marker of these cells. Treatmen t with Pseudomonas aeruginosa LPS resulted in a significant dose-depen dent increase in the basal production of SLPI (+250 +/- 25%) whilst th e SLPI transcript mRNA levels remained unchanged. This LPS-induced inc rease in secretion was inhibited by glucocorticoides. Furthermore, LPS treatment of HTG cells induces a loss of responsiveness to carbachol and isoproterenol but not to adenosine triphosphate. These findings in dicate that HTG cells treated by Pseudomonas aeruginosa LPS have the s ame behavior as those previously observed with CF-HTG cells. Explorati on by using reverse transcriptase polymerase chain reaction amplificat ion showed that LPS down-regulated cystic fibrosis transmembrane condu ctance regulator (CFTR) mRNA expression in HTG cells indicative of a l ink between CFTR function and consequent CF-like alteration in protein secretory process. (C) 1997 Academic Press.