The thermolysin-like metalloproteinase and virulence factor LasB from pathogenic Pseudomonas aeruginosa induces anoikis of human vascular cells

Autor: Beaufort, Nathalie, Corvazier, Elisabeth, Hervieu, Alexia, Choqueux, Christine, Dussiot, Michaël, Louedec, Liliane, Cady, Anne, Bentzmann, Sophie, Michel, Jean-Baptiste, Pidard, Dominique
Přispěvatelé: Clinical Research Unit, Department of Obstetrics and Gynecology, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [Rennes] = Virology [Rennes], CHU Pontchaillou [Rennes], Laboratoire d'ingénierie des systèmes macromoléculaires (LISM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Technical University of Munich (TUM), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7) - Université Paris 13 (UP13) - Université Sorbonne Paris Cité (USPC) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Institut Galilée, Université Paris Diderot - Paris 7 (UPD7) - Institut National de la Santé et de la Recherche Médicale (INSERM), Service de virologie, CHU Pontchaillou [Rennes] - Université de REnne, Aix Marseille Université (AMU) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes]-Université de REnne
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Zdroj: Cellular Microbiology
Cellular Microbiology, 2011, 13 (8), pp.1149--67. ⟨10.1111/j.1462-5822.2011.01606.x⟩
Cellular Microbiology, Wiley, 2011, 13 (8), pp.1149--67. ⟨10.1111/j.1462-5822.2011.01606.x⟩
Cellular Microbiology, Wiley, 2011, 13 (8), pp.1149--67. 〈10.1111/j.1462-5822.2011.01606.x〉
ISSN: 1462-5814
1462-5822
DOI: 10.1111/j.1462-5822.2011.01606.x⟩
Popis: International audience; Disruption of cell/ECM interactions resulting from uncontrolled pericellular proteolysis leads to detachment-induced cell apoptosis (anoikis), contributing to the morbid evolution of inflammatory vascular diseases. During cardiovascular infections, bacterial proteinases might induce vascular cells to enter a similar pathway. We focused on LasB, the predominant metalloproteinase secreted by the haematotropic pathogen Pseudomonas aeruginosa. While the exosecretome of the LasB-deficient pseudomonal strain PAO1lasB? had limited impact on human vascular cell adherence and viability, secretomes from the LasB-expressing reference strain, PAO1, or clinical isolates from patients with cardiac infection all induced anoikis, as did purified LasB. Immunofluorescence and/or immunoblotting analysis of heart valve myofibroblast cultures or whole tissue revealed an extensive, LasB-dependent degradation of ECM-associated fibronectin and vitronectin, that preceded cell de-adherence, whereas type I collagen showed limited degradation. Moreover, LasB produced a rapid endoproteolysis of the cell-associated urokinase receptor/uPAR, leaving a truncated receptor that is unable to support cell adherence and survival via interactions with vitronectin and integrins. Conversely, major myofibroblast integrins showed no or only minor alterations. Thus, among P. aeruginosa-secreted metalloproteinases, LasB can induce vascular cell anoikis through simultaneous proteolysis of ECM components and cell receptors, suggesting the uPAR-vitronectin axis as a major target in this process.
Databáze: OpenAIRE
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