SEPARATION OF LATE BRONCHIAL RESPONSES FROM AIRWAY HYPERRESPONSIVENESS IN ALLERGIC SHEEP

被引:23
作者
SOLER, M [1 ]
SIELCZAK, M [1 ]
ABRAHAM, WM [1 ]
机构
[1] MT SINAI MED CTR,DIV PULM DIS,4300 ALTON RD,MIAMI BEACH,FL 33140
关键词
ASTHMA; ANIMAL MODELS; BRONCHOCONSTRICTION; ALLERGEN; LEUKOTRIENE D4; LEUKOTRIENE D4 ANTAGONIST;
D O I
10.1152/jappl.1991.70.2.617
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Allergic sheep with antigen-induced early and late responses were used to determine whether airway hyperresponsiveness (AHR) to carbachol is present during the late response and whether blocking the late response with the leukotriene D4 (LTD4) antagonist MK-571 also blocks this AHR. To do this, we first showed that MK-571 blocked the antigen-induced late response, and then, in a separate study, we determined the effect of MK-571 treatment on airway responsiveness 6 h after antigen challenge (at the start of the late response). MK-571 (5 mg, by metered dose inhaler) given 30 min before and 4 h after Ascaris suum challenge had no effect on the acute response to antigen but blocked (P < 0.05) the late response compared with placebo (n = 7). In the second study (n = 6), the antigen-induced acute increases in mean specific lung resistance (sRL) were also similar in the placebo (249%) and drug trials (247%). By 6 h postchallenge, however, mean sRL in the placebo trial began to increase (54%, P < 0.05), whereas in the drug trial mean sRL was baseline. Nevertheless, AHR was apparent in both trials as indicated by a mean twofold leftward shift in the dose-response curves to inhaled carbachol (P < 0.05 vs. prechallenge). Bronchoalveolar lavage at 6 h showed that MK-571 did not prevent the inflammatory cell influx into the lung. These observations suggest that although LTD may be a mediator of the late response in sheep, it is not a primary mediator affecting cholinergic AHR during this period.
引用
收藏
页码:617 / 623
页数:7
相关论文
共 38 条
[1]  
ABRAHAM W M, 1989, Pulmonary Pharmacology, V2, P33, DOI 10.1016/S0952-0600(89)80007-9
[2]   CELLULAR MARKERS OF INFLAMMATION IN THE AIRWAYS OF ALLERGIC SHEEP WITH AND WITHOUT ALLERGEN-INDUCED LATE RESPONSES [J].
ABRAHAM, WM ;
SIELCZAK, MW ;
WANNER, A ;
PERRUCHOUD, AP ;
BLINDER, L ;
STEVENSON, JS ;
AHMED, A ;
YERGER, LD .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1988, 138 (06) :1565-1571
[3]  
ABRAHAM WM, 1983, AM REV RESPIR DIS, V128, P839
[4]   A POSSIBLE ROLE FOR PAF IN ALLERGEN-INDUCED LATE RESPONSES - MODIFICATION BY A SELECTIVE ANTAGONIST [J].
ABRAHAM, WM ;
STEVENSON, JS ;
GARRIDO, R .
JOURNAL OF APPLIED PHYSIOLOGY, 1989, 66 (05) :2351-2357
[5]  
ABRAHAM WM, 1988, J PHARMACOL EXP THER, V247, P1004
[6]  
AHMED A, 1989, FASEB Journal, V3, pA438
[7]   ALLERGEN-INDUCED INCREASE IN BRONCHIAL RESPONSIVENESS TO HISTAMINE - RELATIONSHIP TO THE LATE ASTHMATIC RESPONSE AND CHANGE IN AIRWAY CALIBER [J].
CARTIER, A ;
THOMSON, NC ;
FRITH, PA ;
ROBERTS, R ;
HARGREAVE, FE .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1982, 70 (03) :170-177
[8]  
CHUNG KF, 1986, AM REV RESPIR DIS, V134, P258
[9]   CHANGES IN BRONCHIAL RESPONSIVENESS TO HISTAMINE AT INTERVALS AFTER ALLERGEN CHALLENGE [J].
COCKCROFT, DW ;
MURDOCK, KY .
THORAX, 1987, 42 (04) :302-308
[10]   ALLERGEN-INDUCED INCREASE IN NONALLERGIC BRONCHIAL REACTIVITY [J].
COCKCROFT, DW ;
RUFFIN, RE ;
DOLOVICH, J ;
HARGREAVE, FE .
CLINICAL ALLERGY, 1977, 7 (06) :503-513