Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 237K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Adamko, D. J. Articles by Jacoby, D. B. Search for Related Content PubMed PubMed Citation Articles by Adamko, D. J. Articles by Jacoby, D. B. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Dietary Proteins Hazardous Substances DB NITRIC OXIDE Social Bookmarking                            What's this?

Original Article

Darryl J. Adamko^b, Bethany L. Yost^a, Gerald J. Gleich^d, Allison D. Fryer^a, and David B. Jacoby^a,c

^a Department of Environmental Health Sciences, School of Hygiene and Public Health,
^b Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205
^c Department of Internal Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205
^d Department of Immunology and the Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905
Division of Pulmonary and Critical Care Medicine, School of Medicine, Johns Hopkins University, 5501 Hopkins Bayview Circle, Baltimore, MD 21224.410-955-0299410-550-0545

djacoby{at}welchlink.welch.jhu

Asthma exacerbations, many of which are virus induced, are associated with airway eosinophilia. This may reflect altered inflammatory response to viruses in atopic individuals. Inhibitory M₂ muscarinic receptors (M₂Rs) on the airway parasympathetic nerves limit acetylcholine release. Both viral infection and inhalational antigen challenge cause M₂R dysfunction, leading to airway hyperresponsiveness. In antigen-challenged, but not virus-infected guinea pigs, M₂R dysfunction is due to blockade of the receptors by the endogenous antagonist eosinophil major basic protein (MBP). We hypothesized that sensitization to a nonviral antigen before viral infection alters the inflammatory response to viral infection, so that M₂R dysfunction and hyperreactivity are eosinophil mediated. Guinea pigs were sensitized to ovalbumin intraperitoneally, and 3 wk later were infected with parainfluenza. In sensitized, but not in nonsensitized animals, virus-induced hyperresponsiveness and M₂R dysfunction were blocked by depletion of eosinophils with antibody to interleukin (IL)-5 or treatment with antibody to MBP. An additional and unexpected finding was that sensitization to ovalbumin caused a marked (80%) reduction in the viral content of the lungs. This was reversed by the antibody to IL-5, implicating a role for eosinophils in viral immunity.

Key Words: eosinophils • muscarinic receptors • parainfluenza virus • antigen challenge • viral immunity

Some of the data in this manuscript were published previously in abstract form (Adamko, D.J., B.L. Yost, A.D. Fryer, and D.B. Jacoby. 1999. Am. J. Respir. Crit. Care Med. 159:229).

© 1999 The Rockefeller University Press

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS