Down-regulation of canine airway mast cell function following exposure to ozone in vivo.

Abstract

The influence of ozone on the function of airway cells involved in allergic responses is of particular interest due to the increasing prevalence of this environmental oxidant pollutant. In the present studies, the peripheral airways of Ascaris-sensitive dogs were expose to ozone (1 ppm, 5 min) or air (control) and the exposed segments were lavaged 30 min later. The kinetics and magnitude of release of PGD2 and histamine from canine peripheral airway mast cells (PAMC) was determined following in vitro challenge with Ascaris antigen or calcium ionophore approximately 4 h from the time of the in vivo exposures. Histamine content was significantly lower in PAMC retrieved from ozone- versus air-exposed segments (3.0 +/- 0.1 vs. 5.2 +/- 0.5 pg/cell). Absolute release of histamine at 20 min was decreased by 47 and 43% in ozone-exposed cells stimulated with antigen or ionophore, respectively. Maximal synthesis and release of PGD2 in response to antigen (345 +/- 22 pg/10(3) PAMC) or ionophore (1055 +/- 104 pg/10(3) PAMC) was inhibited by 32 and 55%, respectively, in cells from ozone-exposed segments. Inhibition of prostanoid synthesis was not observed in alveolar macrophages in the lavage samples, nor could decreased PGD2 be attributed to enhanced catabolism. These data indicate a differential down-regulatory influence of ozone on subsequent release of granular mediators and newly synthesized PGD2 from PAMC following brief in vivo exposure that lasts for several hours.