title: Relationship of acute lung inflammatory injury to Fas/FasL system.
abstract: 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.
authors.affiliation: Department of Pathology, The University of Michigan Medical School, 1301 Catherine Rd., Ann Arbor, MI 48109-0602, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Neff
authors.forename: Ren-Feng
authors.initials: RF
authors.lastname: Guo
authors.forename: Simona B
authors.initials: SB
authors.lastname: Neff
authors.forename: J Vidya
authors.initials: JV
authors.lastname: Sarma
authors.forename: Cecilia L
authors.initials: CL
authors.lastname: Speyer
authors.forename: Hongwei
authors.initials: H
authors.lastname: Gao
authors.forename: Kurt D
authors.initials: KD
authors.lastname: Bernacki
authors.forename: Markus
authors.initials: M
authors.lastname: Huber-Lang
authors.forename: Stephanie
authors.initials: S
authors.lastname: McGuire
authors.forename: L Marco
authors.initials: LM
authors.lastname: Hoesel
authors.forename: Niels C
authors.initials: NC
authors.lastname: Riedemann
authors.forename: Beatrice
authors.initials: B
authors.lastname: Beck-Schimmer
authors.forename: Firas S
authors.initials: FS
authors.lastname: Zetoune
authors.forename: Peter A
authors.initials: PA
authors.lastname: Ward
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D018893:Bronchoalveolar Lavage; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein; D007074:Immunoglobulin G / Q000737:chemistry; D007249:Inflammation / Q000473:pathology*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D055370:Lung Injury; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000378:metabolism; D009929:Organ Size; D010539:Permeability; D009195:Peroxidase / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D061945:Caspase Inhibitors; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; C404915:Cxcl2 protein, mouse; D004791:Enzyme Inhibitors; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D019014:fas Receptor; D009195:Peroxidase; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases
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