title: In vivo activation of complement by IgA in a rat model.
abstract: In this study we investigated the capacity of rat IgA to activate complement (C) in vivo in a rat model. Rat monomeric (m-), dimeric (d-) and polymeric (p-) IgA MoAbs were injected intravenously and assessed for deposition of C3 and C4 on IgA. By ELISA it was shown that both d- and p-IgA bound C3 whereas no binding of C3 by m-IgA was observed. Polymeric IgA was more efficient in binding of C3 as compared with d-IgA. However, in haemolytic assays no consistent decrease of plasma complement levels was observed except for dimeric IgA which induced a marginal consumption of AP50. When rats were pre-treated with cobra venom factor (CVF) to deplete C3, no C3 deposition was found on m-, d- or p-IgA. Neither m- nor d- or p-IgA was able to bind C4 in vivo. In agreement with the results described above, large sized polymeric IgA was shown to be taken up by Kupffer cells (KC) together with C3. No C3 was detected when rats were depleted of C using CVF. Taken together, the experimental data suggest that d- and p-IgA are able to activate C via the alternative pathway in vivo.
authors.affiliation: Department of Nephrology, University Hospital Leiden, The Netherlands.
authors.forename: R K
authors.initials: RK
authors.lastname: Stad
authors.forename: W M
authors.initials: WM
authors.lastname: Bogers
authors.forename: M E
authors.initials: ME
authors.lastname: Thoomes-van der Sluys
authors.forename: L A
authors.initials: LA
authors.lastname: Van Es
authors.forename: M R
authors.initials: MR
authors.lastname: Daha
mesh_terms: D000818:Animals; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D007070:Immunoglobulin A / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D003176:Complement C3; D007070:Immunoglobulin A; D007074:Immunoglobulin G