BACKGROUND: The Fas/FasL system is both proapoptotic and proinflammatory. FasL is inhibited by decoy receptor-3 (DcR3), a naturally occurring decoy receptor. We determined the effects of systemic blockade of the Fas/FasL system by a DcR3 analog (DcR3-a) in mice with pneumococcal pneumonia. METHODS: Streptococcus pneumoniae (7.2 x 105 or 1.9 x 107 cfu/mL) was instilled intratracheally into untreated C57Bl/6 mice, C57Bl/6 mice treated with DcR3-a, or Fas-deficient lpr mice, and the mice were studied 48 h later. RESULTS: After instillation of the lower bacterial dose, disruption of the Fas/FasL system by either DcR3-a or the lpr mutation resulted in improved clearance of bacteria in the lungs (mean +/- SE, 4.6+/-2.1 x 10(6) and 3.5 +/- 1.6 x 10(6) cfu/lung, respectively, vs. 21.9+/-9.3 x 10(6) cfu/lung in untreated C57Bl/6 mice; P<.05) and decreased percentage of polymorphonuclear neutrophils in bronchoalveolar lavage fluid (mean +/- SE, 19.3%+/-9.5% and 20.2%+/-7.8%, respectively, vs. 55.0%+/-12.2% in untreated C57Bl/6 mice; P<.05). These changes were associated with decreased lung concentrations of the proinflammatory cytokines tumor necrosis factor- alpha and macrophage inflammatory protein-2 and with a decrease in apoptotic cells in the alveolar walls. CONCLUSION: Blockade of the Fas/FasL system by DcR3-a in the lungs improves clearance of bacteria in mice with pneumococcal pneumonia.
BACKGROUND: The Fas/FasL system is both proapoptotic and proinflammatory. FasL is inhibited by decoy receptor-3 (DcR3), a naturally occurring decoy receptor. We determined the effects of systemic blockade of the Fas/FasL system by a DcR3 analog (DcR3-a) in mice with pneumococcal pneumonia. METHODS:Streptococcus pneumoniae (7.2 x 105 or 1.9 x 107 cfu/mL) was instilled intratracheally into untreated C57Bl/6 mice, C57Bl/6 mice treated with DcR3-a, or Fas-deficient lpr mice, and the mice were studied 48 h later. RESULTS: After instillation of the lower bacterial dose, disruption of the Fas/FasL system by either DcR3-a or the lpr mutation resulted in improved clearance of bacteria in the lungs (mean +/- SE, 4.6+/-2.1 x 10(6) and 3.5 +/- 1.6 x 10(6) cfu/lung, respectively, vs. 21.9+/-9.3 x 10(6) cfu/lung in untreated C57Bl/6 mice; P<.05) and decreased percentage of polymorphonuclear neutrophils in bronchoalveolar lavage fluid (mean +/- SE, 19.3%+/-9.5% and 20.2%+/-7.8%, respectively, vs. 55.0%+/-12.2% in untreated C57Bl/6 mice; P<.05). These changes were associated with decreased lung concentrations of the proinflammatory cytokines tumor necrosis factor- alpha and macrophage inflammatory protein-2 and with a decrease in apoptotic cells in the alveolar walls. CONCLUSION: Blockade of the Fas/FasL system by DcR3-a in the lungs improves clearance of bacteria in mice with pneumococcal pneumonia.
Authors: Anne B Lipke; Gustavo Matute-Bello; Raquel Herrero; Kiyoyasu Kurahashi; Venus A Wong; Stephen M Mongovin; Thomas R Martin Journal: J Immunol Date: 2010-03-03 Impact factor: 5.422
Authors: Alex W Farnand; Alison J Eastman; Raquel Herrero; Josiah F Hanson; Steve Mongovin; William A Altemeier; Gustavo Matute-Bello Journal: Am J Respir Cell Mol Biol Date: 2011-01-21 Impact factor: 6.914
Authors: Valerie R Stolberg; Alexandra L McCubbrey; Christine M Freeman; Jeanette P Brown; Sean W Crudgington; Sophina H Taitano; Bridget L Saxton; Peter Mancuso; Jeffrey L Curtis Journal: J Immunol Date: 2015-05-18 Impact factor: 5.422
Authors: Helen M Marriott; Laura E Jackson; Thomas S Wilkinson; A John Simpson; Tim J Mitchell; David J Buttle; Simon S Cross; Paul G Ince; Paul G Hellewell; Moira K B Whyte; David H Dockrell Journal: Am J Respir Crit Care Med Date: 2008-01-17 Impact factor: 21.405
Authors: R A Bem; A W Farnand; V Wong; A Koski; M E Rosenfeld; N van Rooijen; C W Frevert; T R Martin; G Matute-Bello Journal: Am J Physiol Lung Cell Mol Physiol Date: 2008-06-13 Impact factor: 5.464