Regulation of eosinophil trafficking by SWAP-70 and its role in allergic airway inflammation1
Eosinophils are the predominant inflammatory cells recruited to allergic airways. Here we demonstrate 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 mode...
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| Published in: | The Journal of immunology (1950) Vol. 188; no. 3; pp. 1479 - 1490 |
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| Main Authors: | , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
30-12-2011
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| Online Access: | Get full text |
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| Abstract | Eosinophils are the predominant inflammatory cells recruited to allergic airways. Here we demonstrate 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 to WT eosinophils, SWAP-70 deficient (
Swap-70
−/−
) eosinophils revealed altered adhesive interactions within inflamed post capillary 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, compared to WT mice, recruitment of eosinophils to the lungs of allergen-challenged
Swap-70
−/−
mice was significantly reduced along with considerable attenuation of airway inflammation indicated by diminished IL-5, IL-13 and TNFα 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. |
|---|---|
| AbstractList | Eosinophils are the predominant inflammatory cells recruited to allergic airways. Here we demonstrate 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 to WT eosinophils, SWAP-70 deficient (
Swap-70
−/−
) eosinophils revealed altered adhesive interactions within inflamed post capillary 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, compared to WT mice, recruitment of eosinophils to the lungs of allergen-challenged
Swap-70
−/−
mice was significantly reduced along with considerable attenuation of airway inflammation indicated by diminished IL-5, IL-13 and TNFα 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. |
| Author | Ha, Sung Gil Jessberger, Rolf Ge, Xiao Na Kang, Bit Na Blumenthal, Malcolm N. Rao, Savita P. Sriramarao, P. Bahaie, Nooshin S. Hosseinkhani, M. Reza |
| AuthorAffiliation | Department of Medicine, University of Minnesota, St. Paul, MN Laboratory of Allergic Diseases and Inflammation, Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN Institute of Physiological Chemistry, Dresden, Germany |
| AuthorAffiliation_xml | – name: Institute of Physiological Chemistry, Dresden, Germany – name: Laboratory of Allergic Diseases and Inflammation, Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN – name: Department of Medicine, University of Minnesota, St. Paul, MN |
| Author_xml | – sequence: 1 givenname: Nooshin S. surname: Bahaie fullname: Bahaie, Nooshin S. organization: Laboratory of Allergic Diseases and Inflammation, Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN Department of Medicine, University of Minnesota, St. Paul, MN Institute of Physiological Chemistry, Dresden, Germany – sequence: 2 givenname: M. Reza surname: Hosseinkhani fullname: Hosseinkhani, M. Reza organization: Laboratory of Allergic Diseases and Inflammation, Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN Department of Medicine, University of Minnesota, St. Paul, MN Institute of Physiological Chemistry, Dresden, Germany – sequence: 3 givenname: Xiao Na surname: Ge fullname: Ge, Xiao Na organization: Laboratory of Allergic Diseases and Inflammation, Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN Department of Medicine, University of Minnesota, St. Paul, MN Institute of Physiological Chemistry, Dresden, Germany – sequence: 4 givenname: Bit Na surname: Kang fullname: Kang, Bit Na organization: Laboratory of Allergic Diseases and Inflammation, Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN Department of Medicine, University of Minnesota, St. Paul, MN Institute of Physiological Chemistry, Dresden, Germany – sequence: 5 givenname: Sung Gil surname: Ha fullname: Ha, Sung Gil organization: Laboratory of Allergic Diseases and Inflammation, Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN Department of Medicine, University of Minnesota, St. Paul, MN Institute of Physiological Chemistry, Dresden, Germany – sequence: 6 givenname: Malcolm N. surname: Blumenthal fullname: Blumenthal, Malcolm N. organization: Laboratory of Allergic Diseases and Inflammation, Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN Department of Medicine, University of Minnesota, St. Paul, MN Institute of Physiological Chemistry, Dresden, Germany – sequence: 7 givenname: Rolf surname: Jessberger fullname: Jessberger, Rolf organization: Laboratory of Allergic Diseases and Inflammation, Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN Department of Medicine, University of Minnesota, St. Paul, MN Institute of Physiological Chemistry, Dresden, Germany – sequence: 8 givenname: Savita P. surname: Rao fullname: Rao, Savita P. organization: Laboratory of Allergic Diseases and Inflammation, Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN Department of Medicine, University of Minnesota, St. Paul, MN Institute of Physiological Chemistry, Dresden, Germany – sequence: 9 givenname: P. surname: Sriramarao fullname: Sriramarao, P. organization: Laboratory of Allergic Diseases and Inflammation, Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN Department of Medicine, University of Minnesota, St. Paul, MN Institute of Physiological Chemistry, Dresden, Germany |
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| Snippet | Eosinophils are the predominant inflammatory cells recruited to allergic airways. Here we demonstrate that human and murine eosinophils express SWAP-70, an... |
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| Title | Regulation of eosinophil trafficking by SWAP-70 and its role in allergic airway inflammation1 |
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