ORMDL3 promotes eosinophil trafficking and activation via regulation of integrins and CD48

Sung Gil Ha, Xiao Na Ge, Nooshin S. Bahaie, Bit Na Kang, Amrita Rao, Savita P. Rao and P. Sriramarao ()
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Sung Gil Ha: Laboratory of Allergic Diseases and Inflammation, University of Minnesota
Xiao Na Ge: Laboratory of Allergic Diseases and Inflammation, University of Minnesota
Nooshin S. Bahaie: Laboratory of Allergic Diseases and Inflammation, University of Minnesota
Bit Na Kang: Laboratory of Allergic Diseases and Inflammation, University of Minnesota
Amrita Rao: Laboratory of Allergic Diseases and Inflammation, University of Minnesota
Savita P. Rao: Laboratory of Allergic Diseases and Inflammation, University of Minnesota
P. Sriramarao: Laboratory of Allergic Diseases and Inflammation, University of Minnesota

Nature Communications, 2013, vol. 4, issue 1, 1-9

Abstract: Abstract ORM (yeast)-like protein isoform 3 (ORMDL3) has recently been identified as a candidate gene for susceptibility to asthma; however, the mechanisms by which it contributes to asthma pathogenesis are not well understood. Here we demonstrate a functional role for ORMDL3 in eosinophils in the context of allergic inflammation. Eosinophils recruited to the airways of allergen-challenged mice express ORMDL3. ORMDL3 expression in bone marrow eosinophils is localized in the endoplasmic reticulum and is induced by interleukin-3 and eotaxin-1. Overexpression of ORMDL3 in eosinophils causes increased rolling, distinct cytoskeletal rearrangement, extracellular signal-regulated kinase (1/2) phosphorylation and nuclear translocation of nuclear factor kappa B. Knockdown of ORMDL3 significantly inhibits activation-induced cell shape changes, adhesion and recruitment to sites of inflammation in vivo, combined with reduced expression of CD49d and CD18. In addition, ORMDL3 regulates interleukin-3-induced expression of CD48 and CD48-mediated eosinophil degranulation. These studies show that ORMDL3 regulates eosinophil trafficking, recruitment and degranulation, further elucidating a role for this molecule in allergic asthma and potentially other eosinophilic disorders.

Date: 2013
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DOI: 10.1038/ncomms3479

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