Outer Membrane Protein A from Klebsiella pneumoniae Activates Bronchial Epithelial Cells: Implication in Neutrophil Recruitment
Institut National de la Santé et de la Recherche Médicale, Unité 416, Institut Pasteur, Lille, France.The Journal of Immunology (Impact Factor: 4.92). 12/2003; 171(12):6697-705. DOI: 10.4049/jimmunol.171.12.6697
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.
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- "KpOmpA Unfolds and Refolds in Response to Load Structure 20, 121–127, January 11, 2012 ª2012 Elsevier Ltd All rights reserved 123 unfolding events. It may be further speculated that the stepwise unfolding of KpOmpA brings along another advantage that extracellular loops, which facilitate bacterial adhesion (Pichavant et al., 2003; Smith et al., 2007; Wang, 2002), are extracted from potential binding sites as soon as the tensile load applied becomes too high. Our experiments show that the unfolding intermediates of KpOmpA are established by single and grouped b-strands. "
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