title: Mechanisms of isocyanate sensitisation. An in vitro approach.
abstract: Although there is an abundance of clinical evidence which suggests that the inhalation of isocyanates can induce occupational asthma, the immunological basis for the disease is not understood. We have investigated immune cell responses to isocyanate using the cell line mono-mac-6, by measuring the production of hydrogen peroxide, and the expression of ICAM-1 following challenge with isocyanates and their corresponding amines. We observed an increase in the levels of intracellular peroxide, in addition to an upregulation of ICAM-1 expression (P<0.05), following cell stimulation with isocyanates, which was not apparent following stimulation with amines. From the results of this study we hypothesise that the production of reactive oxygen species (ROS) by monocytic cells at the site of exposure to an isocyanate may have two potential outcomes. The first is that the ROS may contribute to tissue damage at the site of inflammation, and then secondly, it is possible this production of hydrogen peroxide may also induce the upregulation of adhesion markers on monocytic cells, specifically ICAM-1, which may potentiate the infiltration and adhesion of cells at the site of inflammation.
authors.affiliation: Health and Safety Laboratory, Broad Lane, S3 7HQ, Sheffield, UK. joanne.elms@hsl.gov.uk
authors.forename: J
authors.initials: J
authors.lastname: Elms
authors.forename: P N
authors.initials: PN
authors.lastname: Beckett
authors.forename: P
authors.initials: P
authors.lastname: Griffin
authors.forename: A D
authors.initials: AD
authors.lastname: Curran
mesh_terms: D003485:Cyanates / Q000633:toxicity*; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D017953:Isocyanates / Q000633:toxicity*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010545:Peroxides / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D014051:Toluene 2,4-Diisocyanate / Q000633:toxicity*; D014407:Tumor Cells, Cultured; D001559:Benzhydryl Compounds
chemical_list: D003485:Cyanates; D018799:Intercellular Adhesion Molecule-1; D017953:Isocyanates; D010545:Peroxides; D014051:Toluene 2,4-Diisocyanate; C015262:1,6-hexamethylene diisocyanate; C005969:4,4'-diphenylmethane diisocyanate; D001559:Benzhydryl Compounds