Differential rates of apoptosis and recruitment limit eosinophil accumulation in the lungs of asthma-resistant CBA/Ca mice.
The accumulation of eosinophils is a common feature of allergic airway inflammation and correlates with disease severity. In an ovalbumin (OVA)-induced murine model of allergic lung disease, CBA/Ca mice develop much lower levels of lung eosinophilia, lung oedema, mucus hypersecretion and airways obstruction than BALB/c and C57BL/6 strains. In this study these strains have been examined to identify mechanisms that control the recruitment and survival of eosinophils in the allergic lung. Following immunization with OVA, CBA/Ca mice developed a robust systemic allergic response, with high levels of total and OVA-specific IgE and increases in peripheral blood eosinophils. Lung eotaxin-1 levels and expression of CD18 on eosinophils recovered by bronchoalveolar lavage (BAL) were least pronounced in CBA/Ca mice, whereas mRNA for L-selectin was highest in eosinophils from C57BL/6 mice. Apoptosis of BAL eosinophils ex vivo was most pronounced in the CBA/Ca strain. BALB/c mice expressed the highest levels of the eosinophil growth and survival factor interleukin (IL)-5 in the lungs and BAL eosinophils from these animals expressed more of the anti-apoptotic proteins Bcl-xL and Bcl-2 than cells from the other strains. A combination of lower levels of recruitment and rapid apoptosis may therefore limit the accumulation of eosinophils and pathology in the lungs of CBA/Ca mice. In addition, although the level of pathology that developed in C57BL/6 and BALB/c mice was similar, some of the underlying mechanisms are likely to differ.
Tumes
Damon J
DJ
School of Molecular and Biomedical Science, University of Adelaide, North Tce, Adelaide 5005, South Australia, Australia.
Wong
Alex C H
AC
Sewell
William A
WA
McColl
Shaun R
SR
Connolly
Ashley
A
Dent
Lindsay A
LA
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001249:Asthma / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D001985:Bronchial Provocation Tests / Q000662:veterinary; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004804:Eosinophils / Q000473:pathology*; D007113:Immunity, Innate / Q000276:immunology*; D007114:Immunization; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008810:Mice, Inbred C57BL / Q000276:immunology; D008808:Mice, Inbred CBA / Q000276:immunology*; D008822:Mice, Transgenic