Decreased airway mucosal prostaglandin E2 production during airway obstruction in an animal model of asthma.
Heaves is a respiratory disorder of horses and ponies characterized by bouts of acute airway obstruction and airway hyperresponsiveness. We measured prostaglandin E2 (PGE2) and 15-hydroxyeicosatetraenoic acid (15-HETE) production in vitro in tracheal epithelium obtained from six affected horses at the time of acute airway obstruction as compared with six matched control horses. Strips of epithelium and subepithelial tissue were prepared and stimulated with A23187, histamine, and bradykinin. The PGE2 and 15-HETE in media from strips was quantitated by radioimmunoassay. 15-HETE above the limits of accurate detection was found in epithelial strips of only two principal animals and in none of the control horses, and the amount of 15-HETE was not increased when strips were stimulated. Epithelial strips from affected horses tended to produce less PGE2 than did strips from control horses, and there was a significant correlation between epithelial PGE2 production and the time taken for affected animals to develop airway obstruction. Subepithelial tissue strips from control horses produced significantly more PGE2 in response to A23187 and bradykinin than did strips from affected horses. We conclude that equine tracheal epithelium is not a significant source of 15-HETE. Airway mucosal PGE2 production is reduced in horses with heaves, which suggests that a relative decrease in this bronchorelaxant substance may be a factor in the pathogenesis of this model of asthma.
Gray
P R
PR
Department of Large Animal Clinical Sciences, Michigan State University, East Lansing 48824-1314.
Derksen
F J
FJ
Broadstone
R V
RV
Robinson
N E
NE
Peters-Golden
M
M
D000402:Airway Obstruction / Q000378:metabolism / Q000503:physiopathology / Q000662:veterinary*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D015232:Dinoprostone / Q000032:analysis / Q000096:biosynthesis*; D004848:Epithelium / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D006734:Horse Diseases / Q000378:metabolism* / Q000503:physiopathology; D006736:Horses; D006893:Hydroxyeicosatetraenoic Acids / Q000032:analysis / Q000096:biosynthesis; D009092:Mucous Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D011863:Radioimmunoassay; D012129:Respiratory Function Tests / Q000379:methods / Q000706:statistics & numerical data / Q000662:veterinary; D014132:Trachea / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
D006893:Hydroxyeicosatetraenoic Acids; D000001:Calcimycin; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D006632:Histamine; D015232:Dinoprostone; D001920:Bradykinin