title: Outer membrane protein A from Klebsiella pneumoniae activates bronchial epithelial cells: implication in neutrophil recruitment.
abstract: Aside from its mechanical barrier function, bronchial epithelium plays an important role both in the host defense and in the pathogenesis of inflammatory airway disorders. To investigate its role in lung defense, the effect of a bacterial cell wall protein, the outer membrane protein A from Klebsiella pneumoniae (kpOmpA) on bronchial epithelial cells (BEC) was evaluated on adhesion molecule expression and cytokine production. Moreover, the potential implication of this mechanism in kpOmpA-induced lung inflammation was also determined. Our in vitro studies demonstrated that kpOmpA strongly bound to BEAS-2B cells, a human BEC line, and to BEC primary cultures, resulting in NF-kappaB signaling pathway activation. Exposure to kpOmpA increased ICAM-1 mRNA and cell surface expression, as well as the secretion of IL-6, CXC chemokine ligand (CXCL)1, CXCL8, C-C chemokine ligand 2, CXCL10 by BEAS-2B cells, and BEC primary cultures (p < 0.005). We analyzed in vivo the consequences of intratracheal injection of kpOmpA to BALB/c mice. In kpOmpA-treated mice, a transient neutrophilia (with a maximum at 24 h) was observed in bronchoalveolar lavage and lung sections. In vivo kpOmpA priming induced bronchial epithelium activation as evaluated by ICAM-1 and CXCL1 expression, associated with the secretion of CXCL1 and CXCL5 in bronchoalveolar lavage fluids. In the lung, an increased level of the IL-6, CXCL1, CXCL5, CXCL10 mRNA was observed with a maximum at 6 h. These data showed that kpOmpA is involved in host defense mechanism by its ability to activate not only APC but also BEC, resulting in a lung neutrophilia.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 416, Institut Pasteur, Lille, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Pichavant
authors.forename: Yves
authors.initials: Y
authors.lastname: Delneste
authors.forename: Pascale
authors.initials: P
authors.lastname: Jeannin
authors.forename: Catherine
authors.initials: C
authors.lastname: Fourneau
authors.forename: Anne
authors.initials: A
authors.lastname: Brichet
authors.forename: André-Bernard
authors.initials: AB
authors.lastname: Tonnel
authors.forename: Philippe
authors.initials: P
authors.lastname: Gosset
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D001980:Bronchi / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D019743:Chemokines, CXC / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D007371:Interferon-gamma / Q000494:pharmacology; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D007442:Intubation, Intratracheal; D007711:Klebsiella pneumoniae / Q000276:immunology* / Q000502:physiology; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000096:biosynthesis; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D001425:Bacterial Outer Membrane Proteins; C515334:CCR2 protein, human; C515335:Ccr2 protein, mouse; D019743:Chemokines, CXC; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C078167:OMPA outer membrane proteins; D007371:Interferon-gamma