Antibody to VLA-4, but not to L-selectin, protects neuronal M2 muscarinic receptors in antigen-challenged guinea pig airways

Allison D. Fryer, Richard W. Costello, Bethany L. Yost, Roy R. Lobb, Thomas F. Tedder, Douglas A. Steeber, Bruce S. Bochner

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

Antigen challenge of sensitized guinea pigs decreases the function of inhibitory M2 muscarinic autoreceptors on parasympathetic nerves in the lung, potentiating vagally induced bronchoconstriction. Loss of M2 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 M2 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 M2 receptor function was tested. In controls, blockade of neuronal M2 muscarinic receptors by gallamine potentiated vagally induced bronchoconstriction, while in challenged animals this effect was markedly reduced, confirming M2 receptor dysfunction. Pretreatment with HP1/2, but not with LAM1-116, protected M2 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 M2 muscarinic receptors, and in so doing, prevents hyperresponsiveness in antigen-challenged guinea pigs.

Original languageEnglish (US)
Pages (from-to)2036-2044
Number of pages9
JournalJournal of Clinical Investigation
Volume99
Issue number8
DOIs
StatePublished - Apr 15 1997

Keywords

  • HP1/2
  • airway hyperresponsiveness
  • eosinophils
  • hyperreactivity
  • inflammation

ASJC Scopus subject areas

  • Medicine(all)

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