Genetic susceptibility to ozone-induced lung inflammation in animal models of asthma

Curr Opin Allergy Clin Immunol. 2004 Oct;4(5):349-53. doi: 10.1097/00130832-200410000-00004.

Abstract

Purpose of review: Epidemiological associations between ozone exposure and allergic responsiveness are well-documented and have been corroborated in animal studies. The complex interaction between ozone and allergen has genetic and environmental components that affect atopic individuals and may increase the incidence of allergy in susceptible individuals. This review describes the advances that have been made in understanding mechanisms of genetic susceptibility to ozone-induced inflammation, and the interaction between ozone and allergen exposure in mice and a non-human primate model.

Recent findings: Antioxidant and innate immune defense genes contribute to ozone-induced inflammation and hyperpermeability in mice and humans. Ozone exposure during the allergic challenge phase induces greater enhancement of allergic responsiveness than the sensitization stage. Ovalbumin-pulsed dendritic cells injected into naïve mice successfully sensitize the mouse to ovalbumin in the absence of adjuvant. Debate continues over the role of T helper 1-T helper 2 immune profile development in mediating the ozone-allergen interaction, and the potential confounding influence of the predominant T helper 2 system most commonly used to study these responses.

Summary: The role of genetic background in susceptibility to ozone-induced lung inflammation has been confirmed, and promising candidate genes have been identified. Descriptive studies confirm that ozone exacerbates allergic responsiveness. Ozone administered during the challenge phase of ovalbumin allergen exposure induces greater responsiveness than during the sensitization phase. Allergen-induced responses enhanced by concurrent ozone exposure warrant further mechanistic research, particularly regarding the influence of susceptibility genes.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Allergens / adverse effects
  • Allergens / genetics
  • Animals
  • Asthma / chemically induced
  • Asthma / etiology
  • Asthma / genetics*
  • Genetic Predisposition to Disease
  • Humans
  • Macaca mulatta
  • Mice
  • Models, Animal
  • Ovalbumin / adverse effects
  • Ovalbumin / genetics
  • Ozone / adverse effects*
  • Pneumonia / chemically induced
  • Pneumonia / etiology
  • Pneumonia / genetics*

Substances

  • Allergens
  • Ozone
  • Ovalbumin