title: Role of the Fas/FasL system in a model of RSV infection in mechanically ventilated mice.
abstract: Infection with respiratory syncytial virus (RSV) in children can progress to respiratory distress and acute lung injury necessitating mechanical ventilation (MV). MV enhances apoptosis and inflammation in mice infected with pneumonia virus of mice (PVM), a mouse pneumovirus that has been used as a model for severe RSV infection in mice. We hypothesized that the Fas/Fas ligand (FasL) system, a dual proapoptotic/proinflammatory system involved in other forms of lung injury, is required for enhanced lung injury in mechanically ventilated mice infected with PVM. C57BL/6 mice and Fas-deficient ("lpr") mice were inoculated intratracheally with PVM. Seven or eight days after PVM inoculation, the mice were subjected to 4 h of MV (tidal volume 10 ml/kg, fraction of inspired O(2) = 0.21, and positive end-expiratory pressure = 3 cm H(2)O). Seven days after PVM inoculation, exposure to MV resulted in less severe injury in lpr mice than in C57BL/6 mice, as evidenced by decreased numbers of polymorphonuclear neutrophils in the bronchoalveolar lavage (BAL), and lower concentrations of the proinflammatory chemokines KC, macrophage inflammatory protein (MIP)-1α, and MIP-2 in the lungs. However, when PVM infection was allowed to progress one additional day, all of the lpr mice (7/7) died unexpectedly between 0.5 and 3.5 h after the onset of ventilation compared with three of the seven ventilated C57BL/6 mice. Parameters of lung injury were similar in nonventilated mice, as was the viral content in the lungs and other organs. Thus, the Fas/FasL system was partly required for the lung inflammatory response in ventilated mice infected with PVM, but attenuation of lung inflammation did not prevent subsequent mortality.
authors: Pediatric Intensive Care Unit, Emma Children’s Hospital, Academic Medical Center, Amsterdam, The Netherlands.
authors: Elske
authors: E
authors: van den Berg
authors: Job B M
authors: JB
authors: van Woensel
authors: Albert P
authors: AP
authors: Bos
authors: Reinout A
authors: RA
authors: Bem
authors: William A
authors: WA
authors: Altemeier
authors: Sean E
authors: SE
authors: Gill
authors: Thomas R
authors: TR
authors: Martin
authors: Gustavo
authors: G
authors: Matute-Bello
mesh_terms: D000818:Animals; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology / Q000821:virology; D054405:Chemokine CCL3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002648:Child; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D029122:Murine pneumonia virus / Q000254:growth & development / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology; D011175:Positive-Pressure Respiration; D012121:Respiration, Artificial; D018357:Respiratory Syncytial Virus Infections / Q000150:complications / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D019014:fas Receptor / Q000172:deficiency* / Q000235:genetics
chemical_list: C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D053222:Fas Ligand Protein; D019014:fas Receptor