title: N-Glycans differentially regulate eosinophil and neutrophil recruitment during allergic airway inflammation.
abstract: Allergic airway inflammation, including asthma, is usually characterized by the predominant recruitment of eosinophils. However, neutrophilia is also prominent during severe exacerbations. Cell surface-expressed glycans play a role in leukocyte trafficking and recruitment during inflammation. Here, the involvement of UDP-N-acetylglucosamine:α-6-D-mannoside β1,6-N-acetylglucosaminyltransferase V (MGAT5)-modified N-glycans in eosinophil and neutrophil recruitment during allergic airway inflammation was investigated. Allergen-challenged Mgat5-deficient (Mgat5(-/-)) mice exhibited significantly attenuated airway eosinophilia and inflammation (decreased Th2 cytokines, mucus production) compared with WT counterparts, attributable to decreased rolling, adhesion, and survival of Mgat5(-/-) eosinophils. Interestingly, allergen-challenged Mgat5(-/-) mice developed airway neutrophilia and increased airway reactivity with persistent elevated levels of proinflammatory cytokines (IL-17A, TNFα, IFNγ)). This increased neutrophil recruitment was also observed in LPS- and thioglycollate (TG)-induced inflammation in Mgat5(-/-) mice. Furthermore, there was significantly increased recruitment of infused Mgat5(-/-) neutrophils compared with WT neutrophils in the peritoneal cavity of TG-exposed WT mice. Mgat5(-/-) neutrophils demonstrated enhanced adhesion to P-selectin as well as increased migration toward keratinocyte-derived chemokine compared with WT neutrophils in vitro along with increased calcium mobilization upon activation and expression of elevated levels of CXCR2, which may contribute to the increased neutrophil recruitment. These data indicate an important role for MGAT5-modified N-glycans in differential regulation of eosinophil and neutrophil recruitment during allergic airway inflammation.
authors.affiliation: Laboratory of Allergic Diseases and Inflammation, Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota 55108.
authors.forename: Nooshin S
authors.initials: NS
authors.lastname: Bahaie
authors.affiliation: Laboratory of Allergic Diseases and Inflammation, Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota 55108.
authors.forename: Bit Na
authors.initials: BN
authors.lastname: Kang
authors.affiliation: Laboratory of Allergic Diseases and Inflammation, Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota 55108.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Frenzel
authors.affiliation: Laboratory of Allergic Diseases and Inflammation, Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota 55108.
authors.forename: M Reza
authors.initials: MR
authors.lastname: Hosseinkhani
authors.affiliation: Laboratory of Allergic Diseases and Inflammation, Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota 55108.
authors.forename: Xiao Na
authors.initials: XN
authors.lastname: Ge
authors.affiliation: Laboratory of Allergic Diseases and Inflammation, Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota 55108.
authors.forename: Yana
authors.initials: Y
authors.lastname: Greenberg
authors.affiliation: Laboratory of Allergic Diseases and Inflammation, Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota 55108.
authors.forename: Sung Gil
authors.initials: SG
authors.lastname: Ha
authors.affiliation: Department of Neurology, Microbiology and Molecular Genetics, Institute for Immunology, University of California, Irvine, California 92697.
authors.forename: Michael
authors.initials: M
authors.lastname: Demetriou
authors.affiliation: Laboratory of Allergic Diseases and Inflammation, Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota 55108.
authors.forename: Savita P
authors.initials: SP
authors.lastname: Rao
authors.affiliation: Laboratory of Allergic Diseases and Inflammation, Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota 55108; Department of Medicine, University of Minnesota, Minneapolis, Minnesota 55455. Electronic address: psrao@umn.edu.
authors.forename: P
authors.initials: P
authors.lastname: Sriramarao
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002241:Carbohydrates / Q000737:chemistry; D002465:Cell Movement; D002633:Chemotaxis; D004804:Eosinophils / Q000378:metabolism*; D006967:Hypersensitivity / Q000378:metabolism; D007249:Inflammation; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000378:metabolism*; D011134:Polysaccharides / Q000737:chemistry*; D018418:Th2 Cells / Q000166:cytology
chemical_list: D002241:Carbohydrates; D011134:Polysaccharides; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase