Differential susceptibility to ozone-induced airways hyperreactivity in inbred strains of mice

Liu Yi Zhang, Roy C Levitt, Steven R. Kleeberger

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Individuals with heightened airways reactivity, such as asthmatics, may be at risk to inflammatory effects of oxidant air pollutants. In the inbred mouse, significant interstrain variation in airways reactivity to acetylcholine (Ach) and differential susceptibility to ozone (O3)-induced airways inflammation has been described previously. This study used these murine models to test hypotheses that (1) O3-induced hyperreactivity to ACh is a function of inherent baseline ACh reactivity, and (2) susceptibility to O3-induced inflammation is associated with O3-induced hyperreactivity. Strains (15-25 g, 6-8 weeks) with HYPERREACTIVE (DBA/2J, AKR/J, A/J), HYPOREACTIVE (C3H/HeJ, C57BL/6J, SJL/J), or INTERMEDIATE (1291]) phenotypes for ACh reactivity were exposed for 3 h to 2.0 ppm O3 or air (control). ACh reactivity (25 and 50 μg/kg, IV) was assessed 0 and 24 h after exposure. Relative to air controls, mean airways responses to 25 and 50 μg/kg ACh 24 h post-O3 increased significantly in the HYPERREACTIVE AIJ strain (p <.05). Among HYPOREACTIVE strains, O3 significantly (p <.05) increased the response to 50 μg/kg ACh in C57BL/6J and SJL/J strains 24 h postexposure. A/J, C57BL/6J, and SJL/J mice are susceptible to O3-induced lung injury. O3 did not alter ACh reactivity in the other strains. O3 also did not affect airways reactivity to methacholine or carbachol, observations consistent with the hypothesis that O3-induced hyperreactivity to ACh may be due, in part, to O3 effects on cholinesterase function. Treatment of C57BL/6J and AIJ mice with an immunosuppressant (cyclophosphamide) or an anti-PMN antibody significantly (p <.05) attenuated circulating and infiltrating polymorphonuclear leukocytes (PMNs), but did not affect O3-induced hyperreactivity. Therefore, O3-induced ACh hyperreactivity was not a function of baseline reactivity, but correlated with susceptibility to acute O3-induced airways injury and inflammation. Pharmacologic studies suggest that although PMNs were associated with O3-induced hyperreactivity, these cells were not the cause of the effect, and that these two events are not codependent.

Original languageEnglish
Pages (from-to)503-518
Number of pages16
JournalExperimental Lung Research
Volume21
Issue number4
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

Fingerprint

Inbred Strains Mice
Ozone
Inflammation
Air
Air Pollutants
Airway Management
Methacholine Chloride
Cholinesterases
Carbachol
Lung Injury
Immunosuppressive Agents
Oxidants
Cyclophosphamide
Acetylcholine
Anti-Idiotypic Antibodies
Neutrophils
Phenotype
Wounds and Injuries
Antibodies
Therapeutics

Keywords

  • Acetylcholine
  • Anti-PMN antibody
  • Asthma
  • Carbachol
  • Genetics
  • Inflammation
  • Methacholine
  • PMN
  • Polymorphonuclear leukocyte

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Differential susceptibility to ozone-induced airways hyperreactivity in inbred strains of mice. / Zhang, Liu Yi; Levitt, Roy C; Kleeberger, Steven R.

In: Experimental Lung Research, Vol. 21, No. 4, 01.01.1995, p. 503-518.

Research output: Contribution to journalArticle

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