Role of the platelet-activating factor (PAF) receptor during pulmonary infection with gram negative bacteria

Authors

  • A C Soares,

    1. Immunopharmacology Laboratory, Departamento de Bioquímica e Imunolgia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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  • V S Pinho,

    1. Immunopharmacology Laboratory, Departamento de Bioquímica e Imunolgia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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  • D G Souza,

    1. Immunopharmacology Laboratory, Departamento de Bioquímica e Imunolgia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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  • T Shimizu,

    1. Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, Japan
    2. CREST of Japan Science and Technology Corporation, Tokyo, Japan
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  • S Ishii,

    1. Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, Japan
    2. CREST of Japan Science and Technology Corporation, Tokyo, Japan
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  • J R Nicoli,

    1. Departamento de Microbiologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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  • M M Teixeira

    Corresponding author
    1. Immunopharmacology Laboratory, Departamento de Bioquímica e Imunolgia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
      Immunofarmacologia, Departamento de Bioquímica e Imunologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Av. Antonio Carlos. 6627 - Pampulha, 31270-901 Belo Horizonte MG Brasil; E-mail: mmtex@icb.ufmg.br
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Immunofarmacologia, Departamento de Bioquímica e Imunologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Av. Antonio Carlos. 6627 - Pampulha, 31270-901 Belo Horizonte MG Brasil; E-mail: mmtex@icb.ufmg.br

Abstract

  • The lipid mediator PAF plays an important role in the phagocytosis of particles, including bacteria, and consequent production of pro-inflammatory cytokines, such as TNF-α and IL-8.

  • Using a PAF receptor antagonist (UK-74,505) and PAF receptor knock-out mice, we have investigated the relevance of PAF for the inflammatory changes and lethality after pulmonary infection with the gram-negative bacteria Klebsiella pneumoniae in mice.

  • At an inoculum of 3×106 bacteria, there was marked pulmonary (bronchoalveolar lavage and lung) neutrophilia that started early (2.5 h after infection) and peaked at 48 h. All animals were dead by day 4 of infection. The chemokine KC and the pro-inflammatory cytokine TNF-α increased rapidly and persisted for 48 h in the lungs.

  • Pretreatment with UK-74,505 (30 mg kg−1 per day, p.o.) had no significant effects on the number of infiltrating neutrophils in BAL fluid or lung tissue, as assessed by histology and measuring myeloperoxidase, or on the concentrations of KC. In contrast, concentrations of TNF-α and the number of bacteria inside neutrophils were significantly diminished.

  • In order to support a role for the PAF during K. pneumoniae infection, experiments were also carried out in PAFR-deficient mice. In the latter animals, lethality occurred earlier than in wild-type controls. This was associated with greater number of bacteria in lung tissue and diminished percentage of neutrophils containing bacteria in their cytoplasm.

  • Our results suggest that PAF, acting on its receptor, plays a protective role during infection with K. pneumoniae in mice.

British Journal of Pharmacology (2002) 137, 621–628. doi:10.1038/sj.bjp.0704918

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