Fas/Fas ligand system mediates epithelial injury, but not pulmonary host defenses, in response to inhaled bacteria.
The Fas/Fas ligand (FasL) system has been implicated in alveolar epithelial cell apoptosis during pulmonary fibrosis and acute respiratory distress syndrome. However, Fas ligation can also lead to cell activation and cytokine production. The goal of this study was to determine the role of the Fas/FasL system in host defenses against Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae. We administered bacteria by aerosolization into the lungs of Fas-deficient (lpr) mice and wild-type (C57BL/6) mice and measured bacterial clearance at 6 and 12 h. One hour prior to euthanasia, the mice received an intraperitoneal injection of human serum albumin (HSA) for alveolar permeability determinations. At all times after bacterial challenges, the lungs of the lpr mice contained similar or lower numbers of bacteria than those of the C57BL/6 mice. Alveolar permeability changes, as determined by bronchoalveolar lavage fluid HSA concentrations, were less severe in the lpr mice 6 h after the challenges. In response to E. coli, the lpr mice had significantly more polymorphonuclear leukocytes (PMN) and macrophage inflammatory protein 2 in the lungs, whereas histopathologic changes were less severe. In contrast, in response to the gram-positive cocci, the lpr animals had similar or lower numbers of PMN. We conclude that the Fas/FasL system contributes to the development of permeability changes and tissue injury during-gram negative bacterial pneumonia. The Fas/FasL system did not have a major role in the clearance of aerosolized bacteria from the lungs at the bacterial doses tested.
Matute-Bello
G
G
Medical Research Service of the VA Puget Sound Health Care System, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.
Frevert
C W
CW
Liles
W C
WC
Nakamura
M
M
Ruzinski
J T
JT
Ballman
K
K
Wong
V A
VA
Vathanaprida
C
C
Martin
T R
TR
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D004926:Escherichia coli / Q000302:isolation & purification / Q000472:pathogenicity; D053222:Fas Ligand Protein; D008168:Lung / Q000276:immunology* / Q000382:microbiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology; D011018:Pneumonia, Pneumococcal / Q000276:immunology / Q000382:microbiology; D011023:Pneumonia, Staphylococcal / Q000276:immunology / Q000382:microbiology; D012709:Serum Albumin / Q000378:metabolism; D013211:Staphylococcus aureus / Q000302:isolation & purification / Q000472:pathogenicity; D013296:Streptococcus pneumoniae / Q000302:isolation & purification / Q000472:pathogenicity; D019014:fas Receptor / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D012709:Serum Albumin; D019014:fas Receptor