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Int Arch Allergy Immunol. 2011;156(2):137-47. doi: 10.1159/000322597. Epub 2011 May 16.

Agonist activation of f-actin-mediated eosinophil shape change and mediator release is dependent on Rac2.

Author information

1
Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, Alta., Canada. paige.lacy@ualberta.ca

Abstract

BACKGROUND:

Tissue recruitment and activation of eosinophils contribute to allergic symptoms by causing airway hyperresponsiveness and inflammation. Shape changes and mediator release in eosinophils may be regulated by mammalian Rho-related guanosine triphosphatases. Of these, Rac2 is essential for F-actin formation as a central process underlying cell motility, exocytosis, and respiratory burst in neutrophils, while the role of Rac2 in eosinophils is unknown.We set out to determine the role of Rac2 in eosinophil mediator release and F-actin-dependent shape change in response to chemotactic stimuli.

METHODS:

Rac2-deficient eosinophils from CD2-IL-5 transgenic mice crossed with rac2 gene knockout animals were examined for their ability to release superoxide through respiratory burst or eosinophil peroxidase by degranulation. Eosinophil shape change and actin polymerization were also assessed by flow cytometry and confocal microscopy following stimulation with eotaxin-2 or platelet-activating factor.

RESULTS:

Eosinophils from wild-type mice displayed inducible superoxide release, but at a small fraction (4-5%) of human eosinophils. Rac2-deficient eosinophils showed significantly less superoxide release (p < 0.05, 26% less than wild type). Eosinophils lacking Rac2 had diminished degranulation (p < 0.05, 62% less eosinophil peroxidase) and shape changes in response to eotaxin-2 or platelet-activating factor (with 68 and 49% less F-actin formation, respectively; p < 0.02) compared with wild-type cells.

CONCLUSION:

These results demonstrate that Rac2 is an important regulator of eosinophil function by contributing to superoxide production, granule protein release, and eosinophil shape change. Our findings suggest that Rho guanosine triphosphatases are key regulators of cellular inflammation in allergy and asthma.

PMID:
21576984
PMCID:
PMC3104871
DOI:
10.1159/000322597
[Indexed for MEDLINE]
Free PMC Article
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