title: Leukotriene generation and metabolism in isolated human lung macrophages.
abstract: We studied the generation and metabolism of leukotrienes (LTs) in human lung macrophages obtained from lung tissue of patients with central bronchial carcinoma. By counterflow centrifugation macrophages were enriched with a purity of more than 95-100%. A time and dose dependent generation of LTB4 and LTC4 was determined by specific radioimmunoassays after stimulation with the Ca-ionophore and anti-IgE. The amount of LTB4 exceeded the amount of LTC4. The concentrations of leukotrienes in the macrophage fraction amounted to 4.3 +/- 2.2 ng LTB4 and 0.6 +/- 0.05 ng LTC4/1 x 10(7) cells after 5 min of incubation with the Ca-ionophore. The LTB4 levels decreased to 3.0 +/- 0.6 ng after 60 min indicating the metabolism of the generated LTB4 by human lung macrophages. This was confirmed by incubation of the cells with exogenously added [3H]LTB4. LTB4 was converted into unpolar products as was identified by thin-layer chromatography and high-performance liquid chromatography; a comparison with the fibroblast cell line L929 which is known to convert LTB4 into the dihydro-LTB4 metabolite (5,12-dihydroxyeicosatrienoic acid) indicates that human lung macrophages use the same pathway of metabolization. Biological inactivation as determined by chemotaxis and cross-reaction with the LTB4 antiserum correlates with the degree of LTB4 metabolism. Moreover, the macrophages convert LTC4 into LTD4 and LTE4 by the enzymatic activity of the gamma-glutamyltranspeptidase and dipeptidase. Our data emphasize that the human alveolar macrophage not only produces arachidonic acid metabolites but modulates the local inflammatory potential by its metabolizing capacity for leukotrienes.
authors.affiliation: Lehrstuhl für Medizinische Mikrobiologie und Immunologie, AG Infektabwehrmechanismen, Ruhr Universität Bochum, FRG.
authors.forename: W
authors.initials: W
authors.lastname: Schönfeld
authors.forename: B
authors.initials: B
authors.lastname: Schlüter
authors.forename: R
authors.initials: R
authors.lastname: Hilger
authors.forename: W
authors.initials: W
authors.lastname: König
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000001:Calcimycin / Q000494:pharmacology; D002283:Carcinoma, Bronchogenic / Q000473:pathology; D002478:Cells, Cultured; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007975:Leukotriene B4 / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008175:Lung Neoplasms / Q000473:pathology; D008264:Macrophages / Q000378:metabolism*; D013189:SRS-A / Q000378:metabolism*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D013189:SRS-A; D007975:Leukotriene B4; D007073:Immunoglobulin E; D000001:Calcimycin