title: Endothelial amine oxidase AOC3 transiently contributes to adaptive immune responses in the airways.
abstract: Amine oxidase, copper containing 3 (AOC3, also known as vascular adhesion protein-1 (VAP-1)) is an endothelial adhesion molecule that contributes to the extravasation of neutrophils, macrophages, and lymphocytes to sites of inflammation. However, the role of AOC3/VAP-1 in allergic responses remains unknown. Here, we studied eosinophil and CD4+ T-cell recruitment to the airways using AOC3/VAP-1-deficient mice. In an OVA-triggered asthma model, AOC3/VAP-1 slightly contributed to the accumulation of leukocytes in lungs in an age-dependent manner. We then established a new model to kinetically measure recruitment of OVA-specific CD4+ T cells to different airway immune compartments during the priming and effector phases of an adaptive immune response. The results showed that in the absence of AOC3/VAP-1, recruitment of antigen-specific CD4+ T cells to draining bronchial lymph nodes is reduced by 89% on day 3 after tracheal allergen exposure, but this difference was not observed on day 6. The dispersal of effector cells to lung and tracheal mucosa is AOC3/VAP-1 independent. Thus, in allergic airway reactions, AOC3/VAP-1 transiently contributes to the antigen-specific, CD4+ T-cell traffic to secondary lymphatic tissues, but not to airway mucosa or lung parenchyma. Our results suggest a largely redundant function for AOC3/VAP-1 in allergic inflammatory responses of the airways.
authors.affiliation: Medicity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Johannes
authors.initials: J
authors.lastname: Dunkel
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Aguilar-Pimentel
authors.forename: Markus
authors.initials: M
authors.lastname: Ollert
authors.forename: Helmut
authors.initials: H
authors.lastname: Fuchs
authors.forename: Valerie
authors.initials: V
authors.lastname: Gailus-Durner
authors.forename: Martin Hrabě
authors.initials: MH
authors.lastname: de Angelis
authors.forename: Sirpa
authors.initials: S
authors.lastname: Jalkanen
authors.forename: Marko
authors.initials: M
authors.lastname: Salmi
authors.forename: Tibor Z
authors.initials: TZ
authors.lastname: Veres
mesh_terms: D056704:Adaptive Immunity; D019264:Adoptive Transfer; D006631:Amine Oxidase (Copper-Containing) / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007962:Leukocytes / Q000276:immunology; D008168:Lung / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology; D014132:Trachea / Q000276:immunology*
chemical_list: D015815:Cell Adhesion Molecules; D010047:Ovalbumin; D006631:Amine Oxidase (Copper-Containing); C492678:semicarbazide-sensitive amine oxidase-vascular adhesion protein-1, mouse
keywords: Adaptive immunity; Adhesion molecules; Airways; Allergy; Leukocyte trafficking