Modulation of mast cell functions by in vitro ozone exposure.
Exposure to ozone has been reported to cause increased immediate bronchial reactivity to inhaled allergen in asthmatics. The purpose of these studies was to determine whether ozone induces either spontaneous physiological degranulation or enhanced immunoglobulin E (IgE)-mediated degranulation of mast cells, thus accounting for the in vivo effects noted in asthmatics. A rat mast cell line (RBL-2H3) was exposed to different levels of ozone (0.1, 0.3, 0.5, and 1.0 ppm), covered by different amounts of buffer, and both cytotoxic and nontoxic exposure conditions were determined. In addition to cytotoxicity, spontaneous release of granule products and prostaglandin D2 (PGD2) associated with ozone exposure were assessed. RBL-2H3 cells were also exposed to ozone under noncytotoxic conditions followed by stimulation with alpha-IgE to cross-link membrane-bound IgE and A23187 so that the effect of ozone on stimulated degranulation could be examined. Only exposure conditions associated with cytotoxicity were associated with spontaneous release of mast cell serotonin, indicating no physiologic degranulation due to ozone exposure. Data presented herein also demonstrate that ozone substantially inhibited both IgE- and A23187-induced degranulation. Neither catalase nor superoxide dismutase protected cells from the inhibitory effect of ozone, indicating that ozone does not act through generation of H2O2 or superoxide. Additionally, ozone caused a modest increase in spontaneous PGD2 generation only under cytotoxic conditions. Thus ozone appears to inhibit mast cell degranulation after IgE- or A23187-mediated stimulation and causes direct release of mast cell granule products and PGD2 only under conditions associated with membrane cytotoxicity.
Peden
D B
DB
Department of Pediatrics, School of Medicine, University of North Carolina-Chapel Hill 27599, USA.
Dailey
L
L
D000818:Animals; D001249:Asthma / Q000503:physiopathology; D000001:Calcimycin / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007073:Immunoglobulin E / Q000494:pharmacology / Q000502:physiology; D007700:Kinetics; D015471:Leukemia, Basophilic, Acute; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D010126:Ozone / Q000494:pharmacology*; D015230:Prostaglandin D2 / Q000378:metabolism; D051381:Rats; D013482:Superoxide Dismutase / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007073:Immunoglobulin E; D000001:Calcimycin; D010126:Ozone; D002374:Catalase; D013482:Superoxide Dismutase; D015230:Prostaglandin D2