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Role of eicosanoids in airflow obstruction and airway plasma exudation induced by trimellitic anhydride‐conjugate in guinea‐pigs 3 and 8 weeks after sensitization
Author(s) -
ARAKAWA H.,
LÖTVALL J.,
LINDÉN A.,
KAWIKOVA I.,
LÖFDAHL C.G.,
SKOOGH B.E.
Publication year - 1994
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.1994.tb00956.x
Subject(s) - pyrilamine , evans blue , extravasation , trimellitic anhydride , sensitization , guinea pig , mepyramine , chemistry , medicine , antagonist , thromboxane a2 , pharmacology , immunology , receptor , polymer chemistry
. Trimellitic anhydride (TMA) is a low molecular weight chemical which can cause occupational asthma. We studied the role of eicosanoids in airway responses to TMA at different times after sensitization in actively sensitized guinea‐pigs. Sensitization was performed by two intradermal injections of free TMA (0.1 ml of 0.3% TMA in corn oil). At 3 and 8 weeks after sensitization, the guinea‐pigs were anaesthetized and challenged with intratracheal instillation of 0.5% TMA conjugated to guinea‐pig serum albumin (TM A‐GPSA; 50 μl). Lung resistance ( R L) was measured to assess airflow obstruction, and the tissue content of Evans Blue dye was measured to assess airway plasma exudation. Intratracheal instillation of TMA‐GPSA induced a slowly progressing increase in R L , reaching a peak at approximately 3.5 min after the challenge (6.0 ± 2.0cm H 2 O/ml/s in the 3‐week group and 3.8 + 0.6 in the 8‐week group). Pretreatment before challenge with pyrilamine (anti‐histamine: 2 mg/kg. intravenously) slowed the onset of the increase in R L following challenge with TMA‐GPSA, and significantly attenuated the peak response. A combination of pyrilamine and IC1‐192, 605 (thromboxane receptor antagonist; 0.5 mg/kg, intravenously) completely abolished the increase in R L in both week groups. A combination of pyrilamine and ICI‐198, 615 (leukotrieneC 4 /D 4 / E 4 receptor antagonist: 0.5 mg/kg, intravenously) did not further attenuate the increase in R L compared with pretreatment with pyrilamine alone, but the induced Evans Blue dye extravasation was completely inhibited in the 3‐week group, whereas a remaining extravasation was observed in the 8‐week group. We conclude that the bronchoconstrictor response to TMA‐GPSA in actively sensitized guinea‐pigs is mediated by histamine and thromboxane A 2 both early and late after sensitization, whereas leukotrienes and histamine partially mediate TMA‐induced airway plasma exudation.