title: Alpha1-antitrypsin inhibits Moraxella catarrhalis MID protein-induced tonsillar B cell proliferation and IL-6 release.
abstract: Alpha1-antitrypsin (AAT) is a major circulating and tissues inhibitor of serine proteinases implicated in the regulation of inflammation and host defence. There is now increasing evidence that AAT may also exhibit anti-inflammatory activities independent of its protease inhibitor function. This study was undertaken to investigate the effects of native (inhibitory) and polymerized (non-inhibitory) forms of AAT on MID (Moraxella IgD binding protein)-induced human tonsillar B cell activation in vitro. We found that 0.5 microg/ml MID induces B cell proliferation and stimulates IL-6 release (p<0.001) relative to non-stimulated controls. Both native and polymerized AAT (0.5 mg/ml) inhibited MID-stimulated B cell proliferation in a similar manner (by 70%, p<0.001), whereas MID-induced IL-6 release was more strongly suppressed by polymerized (9.9-fold, p<0.001) as compared to native AAT (2.8-fold, p<0.01). Electrophoretic analysis of cell culture media did not indicate any interaction between AAT and MID, and flow cytometry data showed no competition for the same receptor. The effects of AATs were observed whether added together with MID or 2h after MID-addition to cell cultures. Thus, our data demonstrate that AAT inhibits MID-induced B cell activation in vitro that is unrelated to its protease inhibitory activity and is not dependent on MID binding to the cell surface.
authors.affiliation: Department of Medical Microbiology, Wallenberg Laboratory, Malmö University Hospital, SE-205 02 Malmö, Sweden.
authors.forename: Radinka
authors.initials: R
authors.lastname: Hadzic
authors.forename: Izabela
authors.initials: I
authors.lastname: Nita
authors.forename: Helena
authors.initials: H
authors.lastname: Tassidis
authors.forename: Kristian
authors.initials: K
authors.lastname: Riesbeck
authors.forename: Anette Gjörloff
authors.initials: AG
authors.lastname: Wingren
authors.forename: Sabina
authors.initials: S
authors.lastname: Janciauskiene
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology* / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology*; D000515:alpha 1-Antitrypsin / Q000494:pharmacology*
chemical_list: D018829:Adhesins, Bacterial; C439616:IgD-binding protein MID, Moraxella catarrhalis; D015850:Interleukin-6; D000515:alpha 1-Antitrypsin