title: LPS-induced 111In-eosinophil accumulation in guinea-pig skin: evidence for a role for TNF-alpha.
abstract: Lipopolysaccharide (LPS) is a major component of the cell wall of Gram-negative bacteria with powerful pro-inflammatory activities. Although the mechanisms involved in LPS-induced neutrophil accumulation have been studied extensively, few reports have focused on the effects of LPS on eosinophil infiltration. In this study we have used an in vivo model of local 111In-eosinophil accumulation in the guinea-pig to investigate the mechanisms of LPS-induced eosinophilia. Using a 4-hr in vivo test period, the intradermal injection of LPS (50-1000 ng/site) led to a marked and dose-dependent accumulation of 111In-eosinophils into guinea-pig skin sites. Time-course experiments revealed that this cell infiltration was delayed in onset, becoming significant 1 hr after the intradermal administration of LPS. The slow development of the response and its sensitivity to the locally administered protein synthesis inhibitor, actinomycin D, suggested that the LPS-induced 111In-eosinophil accumulation in vivo is mediated by the generation of de novo proteins. The intravenous pretreatment of guinea-pigs with a soluble tumour necrosis factor-alpha (TNF-alpha) receptor fusion protein (TNFR-IgG, 1 mg/kg), potently inhibited the 111In-eosinophil accumulation induced by LPS. Our results demonstrate that LPS can induce 111In-eosinophil accumulation in vivo in guinea-pig skin, and that this process is mediated by TNF-alpha.
authors.affiliation: Department of Applied Pharmacology, National Heart & Lung Institute, London.
authors.forename: V B
authors.initials: VB
authors.lastname: Weg
authors.forename: D T
authors.initials: DT
authors.lastname: Walsh
authors.forename: L H
authors.initials: LH
authors.lastname: Faccioli
authors.forename: T J
authors.initials: TJ
authors.lastname: Williams
authors.forename: M
authors.initials: M
authors.lastname: Feldmann
authors.forename: S
authors.initials: S
authors.lastname: Nourshargh
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004802:Eosinophilia / Q000276:immunology*; D004804:Eosinophils / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D007074:Immunoglobulin G; D007205:Indium Radioisotopes; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D012871:Skin Diseases / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D007074:Immunoglobulin G; D007205:Indium Radioisotopes; D008070:Lipopolysaccharides; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin