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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Nooshin S Bahaie - , University of Minnesota System (Autor:in)
  • M Reza Hosseinkhani - (Autor:in)
  • Xiao Na Ge - (Autor:in)
  • Bit Na Kang - (Autor:in)
  • Sung Gil Ha - (Autor:in)
  • Malcolm S Blumenthal - (Autor:in)
  • Rolf Jessberger - , Institut für Physiologische Chemie (Autor:in)
  • Savita P Rao - (Autor:in)
  • P Sriramarao - (Autor:in)

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.

Details

OriginalspracheEnglisch
Seiten (von - bis)1479-1490
Seitenumfang12
FachzeitschriftJournal of Immunology
Jahrgang188
Ausgabenummer3
PublikationsstatusVeröffentlicht - 1 Feb. 2012
Peer-Review-StatusJa

Externe IDs

researchoutputwizard legacy.publication#48938
Scopus 84856575109
PubMed 22210919
PubMedCentral PMC3267576

Schlagworte

Schlagwörter

  • Allergens, Animals, Cell Adhesion, Cell Movement, DNA-Binding Proteins, Eosinophils/pathology, Guanine Nucleotide Exchange Factors, Humans, Inflammation, Mice, Minor Histocompatibility Antigens, Nuclear Proteins, Respiratory Hypersensitivity/etiology, Venules/pathology