CATIONIC PROTEIN-INDUCED SENSORY NERVE ACTIVATION - ROLE OF SUBSTANCE-P IN AIRWAY HYPERRESPONSIVENESS AND PLASMA-PROTEIN EXTRAVASATION

被引:57
作者
COYLE, AJ
PERRETTI, F
MANZINI, S
IRVIN, CG
机构
[1] UNIV COLORADO,HLTH SCI CTR,DEPT MED,DIV PULM SCI,DENVER,CO 80206
[2] NATL JEWISH CTR IMMUNOL & RESP MED,DENVER,CO 80206
[3] MALESCI PHARMACEUT,FLORENCE,ITALY
[4] MENARINI SUD,I-00040 POMEZIA,ITALY
关键词
CATIONIC PROTEINS; AIRWAY HYPERRESPONSIVENESS; SUBSTANCE P; TACHYKININS; PLASMA EXTRAVASATION;
D O I
10.1172/JCI117594
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
We have previously reported that human eosinophil granule major basic protein and synthetic cationic proteins such as poly-L-arginine and poly-L-lysine, can increase airway responsiveness in vivo. In the present study, we have investigated whether activation of sensory C-fibers is important in this phenomenon. Dose-response curves to methacholine were constructed before and 1 h after intratracheal instillation of poly-L-lysine in anaesthetized spontaneously breathing rats, and the concentration of methacholine required to induce a doubling in total lung resistance was calculated. Poly-L-lysine induced a fivefold increase in airway responsiveness, which was inhibited by neonatal capsaicin treatment and potentiated by phosphoramidon (100 mu g/ml). Furthermore, pretreatment with either CP, 96-345, or RP-67580 two selective NK-1 receptor antagonists inhibited poly-L-lysine-induced airway hyperresponsiveness and plasma protein extravasation. In vitro, cationic proteins stimulated the release of calcitonin gene-related peptidelike immunoreactivity from perfused slices of the main bronchi. Our results demonstrate that cationic proteins can activate sensory C-fibers in the airways, an effect which is important in the subsequent development of airway hyperresponsiveness and plasma protein extravasation. Cationic proteins may therefore function as a link between inflammatory cell accumulation and sensory nerve activation.
引用
收藏
页码:2301 / 2306
页数:6
相关论文
共 39 条
[1]  
ACKERMAN SJ, 1983, J IMMUNOL, V131, P2977
[2]   NEW CONCEPTS IN THE PATHOGENESIS OF BRONCHIAL HYPERRESPONSIVENESS AND ASTHMA [J].
BARNES, PJ .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1989, 83 (06) :1013-1026
[3]   NEUROGENIC PLASMA EXTRAVASATION - INHIBITION BY MORPHINE IN GUINEA-PIG AIRWAYS INVIVO [J].
BELVISI, MG ;
ROGERS, DF ;
BARNES, PJ .
JOURNAL OF APPLIED PHYSIOLOGY, 1989, 66 (01) :268-272
[4]  
BERTRAND C, 1993, J IMMUNOL, V151, P4902
[5]  
BERTRAND C, 1993, AM J PHYSIOL, V265, P507
[6]   NEUTRAL ENDOPEPTIDASE AND NEUROGENIC INFLAMMATION IN RATS WITH RESPIRATORY-INFECTIONS [J].
BORSON, DB ;
BROKAW, JJ ;
SEKIZAWA, K ;
MCDONALD, DM ;
NADEL, JA .
JOURNAL OF APPLIED PHYSIOLOGY, 1989, 66 (06) :2653-2658
[7]  
COYLE A J, 1992, American Review of Respiratory Disease, V145, pA38
[8]   CATIONIC PROTEINS ALTER SMOOTH-MUSCLE FUNCTION BY AN EPITHELIUM-DEPENDENT MECHANISM [J].
COYLE, AJ ;
MITZNER, W ;
IRVIN, CG .
JOURNAL OF APPLIED PHYSIOLOGY, 1993, 74 (04) :1761-1768
[9]   CATIONIC PROTEINS INDUCE AIRWAY HYPERRESPONSIVENESS DEPENDENT ON CHARGE INTERACTIONS [J].
COYLE, AJ ;
ACKERMAN, SJ ;
IRVIN, CG .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1993, 147 (04) :896-900
[10]   THE EFFECT OF THE SELECTIVE PAF ANTAGONIST BN 52021 ON PAF-INDUCED AND ANTIGEN-INDUCED BRONCHIAL HYPER-REACTIVITY AND EOSINOPHIL ACCUMULATION [J].
COYLE, AJ ;
URWIN, SC ;
PAGE, CP ;
TOUVAY, C ;
VILLAIN, B ;
BRAQUET, P .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1988, 148 (01) :51-58