Ovalbumin sensitization changes the inflammatory response to subsequent parainfluenza infection

Eosinophils mediate airway hyperresponsiveness, M2 muscarinic receptor dysfunction, and antiviral effects

Darryl J. Adamko, Bethany L. Yost, Gerald J. Gleich, Allison Fryer, David Jacoby

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1465-1477
Number of pages13
JournalJournal of Experimental Medicine
Volume190
Issue number10
DOIs
StatePublished - Nov 15 1999
Externally publishedYes

Fingerprint

Muscarinic M2 Receptors
Paramyxoviridae Infections
Ovalbumin
Eosinophils
Antiviral Agents
Virus Diseases
Viruses
Interleukin-5
Infection
Antigens
Antibodies
Guinea Pigs
Eosinophil Major Basic Protein
Eosinophilia
Acetylcholine
Immunity
Asthma
Lung
Proteins

Keywords

  • Antigen challenge
  • Eosinophils
  • Muscarinic receptors
  • Parainfluenza virus
  • Viral immunity

ASJC Scopus subject areas

  • Immunology

Cite this

@article{6185a122ce0c4ac68a6b6e9269b3ca22,
title = "Ovalbumin sensitization changes the inflammatory response to subsequent parainfluenza infection: Eosinophils mediate airway hyperresponsiveness, M2 muscarinic receptor dysfunction, and antiviral effects",
abstract = "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.",
keywords = "Antigen challenge, Eosinophils, Muscarinic receptors, Parainfluenza virus, Viral immunity",
author = "Adamko, {Darryl J.} and Yost, {Bethany L.} and Gleich, {Gerald J.} and Allison Fryer and David Jacoby",
year = "1999",
month = "11",
day = "15",
doi = "10.1084/jem.190.10.1465",
language = "English (US)",
volume = "190",
pages = "1465--1477",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "10",

}

TY - JOUR

T1 - Ovalbumin sensitization changes the inflammatory response to subsequent parainfluenza infection

T2 - Eosinophils mediate airway hyperresponsiveness, M2 muscarinic receptor dysfunction, and antiviral effects

AU - Adamko, Darryl J.

AU - Yost, Bethany L.

AU - Gleich, Gerald J.

AU - Fryer, Allison

AU - Jacoby, David

PY - 1999/11/15

Y1 - 1999/11/15

N2 - 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.

AB - 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.

KW - Antigen challenge

KW - Eosinophils

KW - Muscarinic receptors

KW - Parainfluenza virus

KW - Viral immunity

UR - http://www.scopus.com/inward/record.url?scp=0033571468&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033571468&partnerID=8YFLogxK

U2 - 10.1084/jem.190.10.1465

DO - 10.1084/jem.190.10.1465

M3 - Article

VL - 190

SP - 1465

EP - 1477

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 10

ER -