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Differential expression and activation of Rab27A in human eosinophils: relationship to blood eosinophilia
Authors:Coughlin Jason J  Odemuyiwa Solomon O  Davidson Courtney E  Moqbel Redwan
Institution:Pulmonary Research Group, Department of Medicine, University of Alberta, 550A Heritage Medical Research Centre, Edmonton, Alberta, Canada T6G 2S2
Abstract:Eosinophil degranulation is thought to play a pathophysiological role in asthma. Rab27A is a GTP-binding protein that is known to be essential for the degranulation of several leukocyte subsets and thus may be essential for eosinophil granule exocytosis. Here, we show that Rab27A mRNA and protein are expressed in human eosinophils. We have developed a novel assay to assess Rab27A activation and have found a similar activation pattern of this protein upon stimulation of eosinophils, neutrophils and NK cells suggesting a similar function in these cell types. Interestingly, Rab27A expression was elevated in eosinophils from asthmatic donors. Furthermore, eosinophils from eosinophilic donors displayed more rapid Rab27A activation kinetics than those from donors with lower eosinophil counts. Given that elevated blood eosinophil numbers correlate with increased priming of eosinophils, this pattern of Rab27A activation suggests differential protein expression in activated cells may allow eosinophils to degranulate more rapidly upon stimulation.
Keywords:Eosinophil  Rab27A  Exocytosis  GTPase  Asthma  Granulocyte  Inflammation
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