Strain-dependent resistance to allergen-induced lung pathophysiology in mice correlates with rate of apoptosis of lung-derived eosinophils

Damon J. Tumes, James Cormie, Michael G. Calvert, Kalev Stewart, Christina Nassenstein, Armin Braun, Paul S. Foster, Lindsay A. Dent

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Although exposed to similar allergic and environmental stimuli, not all humans develop asthma. Similarly, mouse strains vary in the degree of pathophysiology seen following induction of experimental asthma. Three mouse strains (CBA/Ca, BALB/c, and C57BL/6) were used to determine if the extent and duration of inflammation influenced the degree of lung tissue damage in an OVA-induced allergic asthma model. Airways obstruction, leukocyte infiltration, edema, eosinophil accumulation, and degranulation were less severe in wild-type (wt) CBA/Ca mice than wt BALB/c and C57BL/6 mice. F1 hybrids of CBA/Ca mice crossed with BALB/c or C57BL/6 mice had bronchoalveolar lavage leukocyte (BAL) and cell-free protein profiles similar to those of the respective disease-susceptible parental strain. IL-5 transgene expression on each of the three genetic backgrounds accentuated the difference between CBA/Ca and the other two strains. Importantly, even when overexpressing IL-5, CBA/Ca mice did not develop substantial airways obstruction. Eosinophils recovered from the airways of allergic wt and IL-5 transgenic (Tg) CBA/Ca mice entered apoptosis at a faster rate than eosinophils from the other parental strains and F1 hybrids. In contrast, eosinophils harvested from the peritoneal cavities of untreated CBA/Ca IL-5 Tg mice had a relatively low rate of apoptosis in vitro. The CBA/Ca mouse strain is therefore relatively resistant to experimental asthma, and this may be a consequence of a propensity for apoptosis of eosinophils recruited into the allergic lung. Restricting survival of a key effector cell may thus limit pathogenesis in this experimental model and in humans.

Original languageEnglish
Pages (from-to)1362-1373
Number of pages12
JournalJournal of Leukocyte Biology
Volume81
Issue number6
DOIs
Publication statusPublished or Issued - 1 Jun 2007

Keywords

  • Allergy
  • Asthma
  • Inflammation
  • Interleukin 5
  • Necrosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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