Relationship of acute lung inflammatory injury to Fas/FasL system

Am J Pathol. 2005 Mar;166(3):685-94. doi: 10.1016/S0002-9440(10)62290-0.


There is mounting evidence that apoptosis plays a significant role in tissue damage during acute lung injury. To evaluate the role of the apoptosis mediators Fas and FasL in acute lung injury, Fas (lpr)- or FasL (gld)-deficient and wild-type mice were challenged with intrapulmonary deposition of IgG immune complexes. Lung injury parameters ((125)I-albumin leak, accumulation of myeloperoxidase, and wet lung weights) were measured and found to be consistently reduced in both lpr and gld mice. In wild-type mice, lung injury was associated with a marked increase in Fas protein in lung. Inflamed lungs of wild-type mice showed striking evidence of activated caspase-3, which was much diminished in inflamed lungs from lpr mice. Intratracheal administration of a monoclonal Fas-activating antibody (Jo2) in wild-type mice induced MIP-2 and KC production in bronchoalveolar lavage fluids, and a murine alveolar macrophage cell line (MH-S) showed significantly increased MIP-2 production after incubation with this antibody. Bronchoalveolar lavage fluid content of MIP-2 and KC was substantially reduced in lpr mice after lung injury when compared to levels in wild-type mice. These data suggest that the Fas/FasL system regulates the acute lung inflammatory response by positively affecting CXC-chemokine production, ultimately leading to enhanced neutrophil influx and tissue damage.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis
  • Blotting, Western
  • Bronchoalveolar Lavage
  • Caspase 3
  • Caspase Inhibitors
  • Caspases / metabolism
  • Cell Line
  • Chemokine CXCL2
  • Chemokines / metabolism
  • Chemokines, CXC / metabolism*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Fas Ligand Protein
  • Immunoglobulin G / chemistry
  • Inflammation / pathology*
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology*
  • Lung Injury
  • Macrophages / metabolism
  • Male
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / metabolism
  • Organ Size
  • Permeability
  • Peroxidase / metabolism
  • fas Receptor / metabolism*


  • Caspase Inhibitors
  • Chemokine CXCL2
  • Chemokines
  • Chemokines, CXC
  • Cxcl2 protein, mouse
  • Enzyme Inhibitors
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Immunoglobulin G
  • Membrane Glycoproteins
  • fas Receptor
  • Peroxidase
  • Casp3 protein, mouse
  • Caspase 3
  • Caspases