Regulation of eosinophil trafficking by SWAP-70 and its role in allergic airway inflammation

Nooshin S. Bahaie, M. Reza Hosseinkhani, Xiao Na Ge, Bit Na Kang, Sung Gil Ha, Malcolm S. Blumenthal, Rolf Jessberger, Savita P. Rao, P. Sriramarao

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Eosinophils are the predominant inflammatory cells recruited to allergic airways. In this article, we show that human and murine eosinophils express SWAP-70, an intracellular RAC-binding signaling protein, and examine its role in mediating eosinophil trafficking and pulmonary recruitment in a murine model of allergic airway inflammation. Compared with wild-type eosinophils, SWAP-70-deficient (Swap-70 -/-) eosinophils revealed altered adhesive interactions within inflamed postcapillary venules under conditions of blood flow by intravital microscopy, exhibiting enhanced slow rolling but decreased firm adhesion. In static adhesion assays, Swap-70 -/- eosinophils adhered poorly to VCAM-1 and ICAM-1 and exhibited inefficient leading edge and uropod formation. Adherent Swap-70 -/- eosinophils failed to translocate RAC1 to leading edges and displayed aberrant cell surface localization/distribution of α4 and Mac-1. Chemokine-induced migration of Swap-70 -/- eosinophils was significantly decreased, correlating with reduced intracellular calcium levels, defective actin polymerization/ depolymerization, and altered cytoskeletal rearrangement. In vivo, recruitment of eosinophils to the lungs of allergen-challenged Swap-70 -/- mice, compared with wild-type mice, was significantly reduced, along with considerable attenuation of airway inflammation, indicated by diminished IL-5, IL-13, and TNF-α levels; reduced mucus secretion; and improved airway function. These findings suggest that regulation of eosinophil trafficking and migration by SWAP-70 is important for the development of eosinophilic inflammation after allergen exposure.

Original languageEnglish (US)
Pages (from-to)1479-1490
Number of pages12
JournalJournal of Immunology
Volume188
Issue number3
DOIs
StatePublished - Feb 1 2012

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