Antigen-induced mediator release in primates.
We examined the release of bronchoactive mediators into the airways of allergic primates during the acute response to specific antigen inhalation. Twelve adult male cynomolgus monkeys (Macaca fascicularis) with a naturally occurring respiratory sensitivity to inhaled Ascaris suum extract were anesthetized and intubated for each study. Respiratory system resistance (Rrs) and dynamic lung compliance (CLdyn) were measured before and after antigen inhalation, and the release of mediators into the airways was assessed by bronchoalveolar lavage (BAL). BAL samples were concentrated approximately 5-fold before quantitation of LTC4 and PGD2 by RP-HPLC and radioimmunoassay and histamine by a fluorometric assay. Antigen inhalation resulted in a 40-fold increase in BAL levels of i-LTC4 (1.5 +/- 0.7 to 41.6 +/- 12.7 ng, p less than 0.01), a 10-fold increase in i-PGD2 (2.4 +/- 0.9 to 25.9 +/- 5.5 ng, p less than 0.01), and a 20-fold increase in BAL histamine (1.0 +/- 1.5 to 21.4 +/- 2.3 micrograms, p less than 0.01). Dexamethasone (n = 7) inhibited the antigen-induced increase in BAL i-LTC4 (71 +/- 6%, p less than 0.01) and i-PGD2 (52 +/- 8%, p less than 0.05) while weakly inhibiting histamine release (43 +/- 10%). Indomethacin (n = 7) had a variable effect on i-LTC4 levels (6 +/- 51%), strongly inhibited i-PGD2 (88 +/- 9%, p less than 0.01), and had no effect on histamine release (25 +/- 8%). Pretreatment with iodoxamide tromethamine significantly blocked the release of each mediator, but mepyramine, an H1 antagonist, had no effect on mediator release.(ABSTRACT TRUNCATED AT 250 WORDS)
Gundel
R H
RH
Department of Pharmacology, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut 06877.
Kinkade
P
P
Torcellini
C A
CA
Clarke
C C
CC
Watrous
J
J
Desai
S
S
Homon
C A
CA
Farina
P R
PR
Wegner
C D
CD
D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D001200:Ascaris / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000473:pathology; D016084:Bronchoconstriction / Q000187:drug effects; D002452:Cell Count; D002851:Chromatography, High Pressure Liquid; D003907:Dexamethasone / Q000494:pharmacology; D006632:Histamine / Q000032:analysis; D007975:Leukotriene B4 / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism*; D008055:Lipids / Q000502:physiology; D008170:Lung Compliance / Q000187:drug effects; D008252:Macaca fascicularis; D008297:Male; D015230:Prostaglandin D2 / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D011738:Pyrilamine / Q000494:pharmacology; D012130:Respiratory Hypersensitivity / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013189:SRS-A / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism
D000941:Antigens; D015289:Leukotrienes; D008055:Lipids; D011453:Prostaglandins; D013189:SRS-A; D007975:Leukotriene B4; D013929:Thromboxane B2; D003907:Dexamethasone; D006632:Histamine; D011738:Pyrilamine; D015230:Prostaglandin D2