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Published online before print March 12, 2004
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,1
* Division of Molecular Biosciences, John Curtin School of Medical Research, Australian National University, Canberra;
School of Biomedical Sciences, Faculty of Health, University of Newcastle, Australia;
Department of Biochemistry and Molecular Biology, Mayo Clinic, Scottsdale, Arizona; and
Department of Molecular Biosciences, University of Adelaide, Australia
1 Correspondence: Division of Molecular Biosciences, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, 0200, Australia. E-mail: Paul.Foster{at}anu.edu.au and School of Biomedical Sciences, Faculty of Health, University of Newcastle, Newcastle, NSW, Australia 2300. E-mail: Paul.Foster{at}newcastle.edu.au
Eosinophil degranulation is thought to play a pivotal role in the pathogenesis of allergic disorders. Although mouse models of allergic disorders have been used extensively to identify the contribution of eosinophils to disease, ultrastructural evidence of active granule disassembly has not been reported. In this investigation, we characterized the degree of eosinophil activation in the bone marrow, blood, lung tissue, and airways lumen [bronchoalveolar lavage fluid (BALF)] of ovalbumin-sensitized and aero-challenged wild-type and interleukin-5 transgenic mice. Degranulation was most prominent in and primarily compartmentalized to the airways lumen. Eosinophils released granule proteins by the process of piecemeal degranulation (PMD). Accordingly, recruitment and activation of eosinophils in the lung correlated with the detection of cell-free eosinophil peroxidase in BALF and with the induction of airways hyper-reactivity. As in previous studies with human eosinophils, degranulation of isolated mouse cells did not occur until after adherence to extracellular matrix. However, higher concentrations of exogenous stimuli appear to be required to trigger adherence and degranulation (piecemeal) of mouse eosinophils when compared with values reported for studies of human eosinophils. Thus, mouse eosinophils undergo PMD during allergic inflammation, and in turn, this process may contribute to pathogenesis. However, the degranulation process in the allergic lung of mice is primarily compartmentalized to the airway lumen. Understanding the mechanism of eosinophil degranulation in the airway lumen may provide important insights into how this process occurs in human respiratory diseases.
Key Words: asthma • cellular activation • eosinophil
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