title: Roles of tumor necrosis factor receptor signaling during murine Escherichia coli pneumonia.
abstract: We hypothesized that tumor necrosis factor (TNF)-alpha signaling is essential to inflammation and host defense during Escherichia coli pneumonia. We tested this hypothesis by instilling E. coli into the lungs of wild-type (WT) mice and gene-targeted mice that lack both p55 and p75 receptors for TNF-alpha. The emigration of neutrophils 6 h after instillation of E. coli was not decreased, but rather was significantly increased (167% of WT), in TNF receptor (TNFR)-deficient mice. This increased neutrophil emigration did not result from peripheral blood neutrophilia or enhanced neutrophil sequestration, inasmuch as the numbers of neutrophils in the circulating blood and in the pulmonary capillaries did not differ between TNFR-deficient and WT mice. The accumulation of pulmonary edema fluid was not inhibited in TNFR-deficient compared with WT mice. Nuclear factor-kappaB (NF-kappaB) translocation in the lungs was not prevented in TNFR-deficient mice. Thus, signaling pathways independent of TNFRs can mediate the acute inflammatory response during E. coli pneumonia. However, despite this inflammatory response, bacterial clearance was impaired in TNFR-deficient mice (109 +/- 8% versus 51 +/- 14% of the original inoculum viable after 6 h in TNFR-deficient and WT mice, respectively). Increased neutrophil emigration during E. coli pneumonia in TNFR-deficient mice may thus result from an increased bacterial burden in the lungs. During acute E. coli pneumonia, the absence of TNFR signaling compromised bacterial killing, but did not prevent inflammation, as measured by the accumulation of edema fluid and neutrophils.
authors.affiliation: Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Mizgerd
authors.forename: J J
authors.initials: JJ
authors.lastname: Peschon
authors.forename: C M
authors.initials: CM
authors.lastname: Doerschuk
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D001692:Biological Transport; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000378:metabolism* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II