Antibody to VLA-4, but not to L-selectin, protects neuronal M-2 muscarinic receptors in antigen-challenged guinea pig airways

被引:71
作者
Fryer, AD
Costello, RW
Yost, BL
Lobb, RR
Tedder, TF
Steeber, DA
Bochner, BS
机构
[1] JOHNS HOPKINS UNIV,DEPT MED,DIV CLIN IMMUNOL,BALTIMORE,MD 21205
[2] BIOGEN INC,CAMBRIDGE,MA 02142
[3] DUKE UNIV,MED CTR,DEPT IMMUNOL,DURHAM,NC 27710
关键词
airway hyperresponsiveness; eosinophils; HP1/2; hyperreactivity; inflammation;
D O I
10.1172/JCI119372
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
Antigen challenge of sensitized guinea pigs decreases the function of inhibitory M-2 muscarinic autoreceptors on parasympathetic nerves in the lung, potentiating vagally induced bronchoconstriction. Loss of M-2 receptor function is associated with the accumulation of eosinophils around airway nerves. To determine whether recruitment of eosinophils via expression of VLA-4 and L-selectin is critical for loss of M-2 receptor function, guinea pigs were pretreated with monoclonal antibodies to VLA-4 (HP1/2) or L-selectin (LAM1-116). Guinea pigs were sensitized and challenged with ovalbumin, and M-2 receptor function was tested. In controls, blockade of neuronal M-2 muscarinic receptors by gallamine potentiated vagally induced bronchoconstriction, while in challenged animals this effect was markedly reduced, confirming M-2 receptor dysfunction. Pretreatment with HP1/2, but not with LAM1-116, protected M-2 receptor function in the antigen-challenged animals. HP1/2 also inhibited the development of hyperresponsiveness, and selectively inhibited accumulation of eosinophils in the lungs as measured by lavage and histology. Thus, inhibition of eosinophil influx into the lungs protects the function of M-2 muscarinic receptors, and in so doing, prevents hyperresponsiveness in antigen-challenged guinea pigs.
引用
收藏
页码:2036 / 2044
页数:9
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