The eosinophil in airway remodelling and hyperresponsiveness in asthma: participant or bystander?
http://www.100md.com
《胸》
Respirology Resident, McMaster University, Hamilton, Canada; msoth@idirect.com
Lee JJ, Dimina D, Macias MP, et al. Defining a link with asthma in mice congenitally deficient in eosinophils. Science 2004;305:1773–6
Humbles AA, Lloyd CM, McMillan SJ, et al. A critical role for eosinophils in allergic airways remodelling. Science 2004;305:1776–9
While the presence of eosinophils in asthma has long been recognised, it remains unclear whether they are directly involved in the pathogenesis of asthma or are merely an epiphenomenon. Both Lee et al and Humbles et al used an acute inhaled allergen challenge with ovalbumin as a model of asthma. Lee et al used mice that expressed diphtheria toxin A in eosinophils (PHIL mice) resulting in eosinophil apoptosis while Humble et al used mice with mutations in a transcription factor (GATA-1 mice) that selectively prevented the differentiation of myeloid cells into eosinophils. Both mutants were essentially devoid of eosinophils with preservation of other leucocytes.
Compared with wild type mice, the PHIL mice had reduced epithelial hypertrophy and goblet cell metaplasia while the GATA-1 mice had decreased airway smooth muscle proliferation and fibrin deposition. This suggests that eosinophils have an important role in airway remodelling.
The PHIL mice were completely protected from developing airway hyperresponsiveness following allergen challenge, suggesting a key role for eosinophils, while the GATA-1 mice had enhanced airway hyperresponsiveness following allergen challenge which suggests that eosinophils were not essential. The difference in response may have been due to the fact that the mice were developed from different background strains. Asthma is a multigenic disease and the importance of eosinophils in the pathogenesis of asthma may vary depending on the rest of the subject’s genetic makeup. This could have important therapeutic implications. Targeted suppression of eosinophils may help to attenuate airway remodelling, but may only affect airway hyperresponsiveness in some asthma patients with the right genetic background.(M Soth)
Lee JJ, Dimina D, Macias MP, et al. Defining a link with asthma in mice congenitally deficient in eosinophils. Science 2004;305:1773–6
Humbles AA, Lloyd CM, McMillan SJ, et al. A critical role for eosinophils in allergic airways remodelling. Science 2004;305:1776–9
While the presence of eosinophils in asthma has long been recognised, it remains unclear whether they are directly involved in the pathogenesis of asthma or are merely an epiphenomenon. Both Lee et al and Humbles et al used an acute inhaled allergen challenge with ovalbumin as a model of asthma. Lee et al used mice that expressed diphtheria toxin A in eosinophils (PHIL mice) resulting in eosinophil apoptosis while Humble et al used mice with mutations in a transcription factor (GATA-1 mice) that selectively prevented the differentiation of myeloid cells into eosinophils. Both mutants were essentially devoid of eosinophils with preservation of other leucocytes.
Compared with wild type mice, the PHIL mice had reduced epithelial hypertrophy and goblet cell metaplasia while the GATA-1 mice had decreased airway smooth muscle proliferation and fibrin deposition. This suggests that eosinophils have an important role in airway remodelling.
The PHIL mice were completely protected from developing airway hyperresponsiveness following allergen challenge, suggesting a key role for eosinophils, while the GATA-1 mice had enhanced airway hyperresponsiveness following allergen challenge which suggests that eosinophils were not essential. The difference in response may have been due to the fact that the mice were developed from different background strains. Asthma is a multigenic disease and the importance of eosinophils in the pathogenesis of asthma may vary depending on the rest of the subject’s genetic makeup. This could have important therapeutic implications. Targeted suppression of eosinophils may help to attenuate airway remodelling, but may only affect airway hyperresponsiveness in some asthma patients with the right genetic background.(M Soth)