Perforin - 2 is essential for intracellular defense of parenchymal cells and phagocytes against 1 pathogenic bacteria

نویسندگان

  • Ryan M. McCormack
  • Lesley R. de Armas
  • Motoaki Shiratsuchi
  • Desirée G. Fiorentino
  • Mathias G. Lichtenheld
  • Alejo Morales
  • Kirill Lyapichev
  • Louis E. Gonzalez
  • Neelima Sukumar
  • Olivera Stojadinovic
  • Gregory V. Plano
  • George P. Munson
  • Robert S. Kirsner
  • David G. Russell
  • Eckhard R. Podack
چکیده

19 Perforin-2 (MPEG1) is a pore-forming, antibacterial protein with broad-spectrum activity. Perforin-2 is 20 expressed constitutively in phagocytes and inducibly in parenchymal, tissue-forming cells. In vitro, 21 Perforin-2 prevents the intracellular replication and proliferation of bacterial pathogens in these cells. 22 Perforin-2 knockout mice are unable to control the systemic dissemination of methicillin-resistant 23 Staphylococcus aureus (MRSA) or Salmonella typhimurium and perish shortly after epicutaneous or 24 orogastric infection respectively. In contrast, Perforin-2-sufficient littermates clear the infection. 25 Perforin-2 is a transmembrane protein of cytosolic vesicles-derived from multiple organelles-that 26 translocate to and fuse with bacterium containing vesicles. Subsequently, Perforin-2 polymerizes and 27 forms large clusters of 100Å pores in the bacterial surface with Perforin-2 cleavage products present 28 in bacteria. Perforin-2 is also required for the bactericidal activity of reactive oxygen and nitrogen 29 species and hydrolytic enzymes. Perforin-2 constitutes a novel and apparently essential bactericidal 30 effector molecule of the innate immune system.

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Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria

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تاریخ انتشار 2015