title: Pseudomonas stimulates interleukin-8 mRNA expression selectively in airway epithelium, in gland ducts, and in recruited neutrophils.
abstract: Neutrophils may play important roles in chronic airway diseases. Pseudomonas is a common pathogen in some chronic airway diseases, and expression of the neutrophil chemoattractant interleukin-8 (IL-8) is induced by Pseudomonas in various cells in vitro. Here we examine the localization of IL-8 mRNA expression after incubating human and dog bronchi with Pseudomonas supernatant in vitro. To examine IL-8 expression in recruited neutrophils, we also superfused the dog bypassed tracheal segment with Pseudomonas supernatant in vivo and measured neutrophil number and IL-8 concentration in luminal fluid; simultaneously, we introduced Pseudomonas supernatant by catheter in a peripheral airway. After 6 h, we analyzed IL-8 mRNA expression and localization in removed tissue. Unincubated bronchi showed no IL-8 mRNA expression, but incubation with Pseudomonas supernatant in vitro resulted in IL-8 mRNA expression in surface epithelial, gland duct, and a subpopulation of serous gland cells. In vivo, introduction of Pseudomonas supernatant into dog trachea and peripheral airways caused IL-8 mRNA expression in epithelial and gland duct cells but also in the recruited neutrophils. Pseudomonas lipopolysaccharide alone was without effect in vitro and in vivo. We conclude that Pseudomonas products, but not lipopolysaccharide, stimulate IL-8 expression in airways and that this expression occurs primarily in surface epithelial and gland duct cells, thus bringing the chemoattractant to the bacterial site. Furthermore, IL-8 expression in recruited neutrophils provides a potential mechanism for positive feedback of this protective antibacterial response.
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
authors.forename: H
authors.initials: H
authors.lastname: Inoue
authors.forename: P P
authors.initials: PP
authors.lastname: Massion
authors.forename: I F
authors.initials: IF
authors.lastname: Ueki
authors.forename: K M
authors.initials: KM
authors.lastname: Grattan
authors.forename: M
authors.initials: M
authors.lastname: Hara
authors.forename: A F
authors.initials: AF
authors.lastname: Dohrman
authors.forename: B
authors.initials: B
authors.lastname: Chan
authors.forename: J A
authors.initials: JA
authors.lastname: Lausier
authors.forename: J A
authors.initials: JA
authors.lastname: Golden
authors.forename: J A
authors.initials: JA
authors.lastname: Nadel
mesh_terms: D000328:Adult; D000818:Animals; D001483:Base Sequence; D001980:Bronchi / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D046508:Culture Techniques; D004285:Dogs; D004847:Epithelial Cells; D005088:Exocrine Glands / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008875:Middle Aged; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000473:pathology; D009504:Neutrophils / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D014132:Trachea / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016209:Interleukin-8; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha