title: Lipopolysaccharide-induced lung injury: role of P2X7 receptor.
abstract: BACKGROUND
  P2X7 receptors have been involved in inflammatory and immunological responses, and their activation modulates pro-inflammatory cytokines production by LPS-challenged macrophages.
  
  
  OBJECTIVE
  To determine the role of P2X7R in LPS-induced acute lung injury in mice.
  
  
  METHODS
  Wild-type (C57BL/6) and P2X7 knockout mice received intratracheal injection of saline or Escherichia coli LPS (60 μg). After 24h, changes in lung mechanics were determined by the end-inflation occlusion method. Bronchoalveolar lavage was performed, and lungs were harvested for measurement of morphometry, fibers content, inflammatory cells and cytokine expression by histochemistry and immunohistochemistry.
  
  
  RESULTS
  Compared with saline, LPS increased lung mechanical parameters, mast cell, collagen and fibronectin deposition in lung parenchyma, as well as nitric oxide and lactate dehydrogenase release into bronchoalveolar fluid in wild-type, but not in P2X7R knockout mice. Alveolar collapse, lung influx of polymorphonuclear and CD14(+) cells, as well as TGF-β, MMP-2, and IL-1β release were higher in wild-type than knockout LPS-challenged mice, while MMP-9 release where similar between the two genotypes. LPS increased macrophage immunoreactivity in lung tissue in both genotypes, but macrophages were not activated in the P2X7R knockout mice. Furthermore, LPS administration increased P2X7R immunoexpression in lung parenchyma in wild-type mice, and TLR4 in both wild-type and P2X7R knockout mice.
  
  
  CONCLUSIONS
  P2X7 receptors are implicated in the pathophysiology of LPS-induced lung injury, modulating lung inflammatory and functional changes.
authors: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Leonardo C
authors: LC
authors: Monção-Ribeiro
authors: Viviane R
authors: VR
authors: Cagido
authors: Graziela
authors: G
authors: Lima-Murad
authors: Patricia Teixeira
authors: PT
authors: Santana
authors: Douglas R
authors: DR
authors: Riva
authors: Radovan
authors: R
authors: Borojevic
authors: Walter A
authors: WA
authors: Zin
authors: Moises C M
authors: MC
authors: Cavalcante
authors: Ingred
authors: I
authors: Riça
authors: Aline Cristina
authors: AC
authors: Brando-Lima
authors: Christina M
authors: CM
authors: Takiya
authors: Débora S
authors: DS
authors: Faffe
authors: Robson
authors: R
authors: Coutinho-Silva
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D015656:Respiratory Mechanics / Q000502:physiology
chemical_list: D008070:Lipopolysaccharides; D058486:Receptors, Purinergic P2X7