Elimination of circulation IgA and IgS immune complexes: An experimental study in mice, rats and guinea pigs
1995 (English)Doctoral thesis, comprehensive summary (Other academic)
Immune complexes were formed between dinitrophenyl- (DNP-) conjugated human serum albumin (HSA) and anti-DNP antibodies (monoclonal mouse IgA or polyclonal rabbit IgG). Blood clearance and tissue distribution of intravenously injected labelled antigen and immunecomplex preparations were studied in mice, rats and guinea pigs. Interaction between immune complexes and liver cells were also studied in vitro. Although neither IgG nor IgA had any great influence on the antigen blood clearance kinetics, both of the antibody preparations had influence on the hepatic uptake.
IgG immune complexes were taken up very efficiently by the rat liver and to some extent by the spleen. IgA immune complexes were taken up by the liver in both rats and guinea pigs, although far less efficiently.
In rats about 90% of the intravenously injected IgG immune complexes were recovered from the Kupffer cells and 8% from the liver endothelial cells, whereas only minor amounts were found in the hepatocytes. The IgG immune complexes were degraded to about the same relative extent by both Kupffer cells and liver endothelial cells. In vitro the quantitativeuptake and degradation of IgG immune complexes was similar in Kupffer cells and liver endothelial cells. The binding of IgG immune complexes to Kupffer cells and liver endothelial cells was saturable and blocked by preincubation with unlabelled IgG immune complexes, indicating Fc-receptor mediated uptake. Our results suggest that Kupffer cellsnormally eliminate most circulating IgG immune complexes, but that the liver endothelial cells may constitute an important reserve capacity. Also in vitro, the binding ofigG immune complexes by hepatocytes was negligible, and these cells do not seem to be of importance for the handling of IgG immune complexes.
Kupffer cells, but not liver endothelial cells, were found to release H202 in response to lgG immune complexes. Further, H202 was found to decrease the association of uncomplexed antigen to both Kupffer cells and liver endothelial cells but had no effect on the association of IgG imrmme complexes in vitro.
In vivo, IgA increased the antigen localisation to the hepatocytes in rats, but not in guinea pigs. This difference is probably explained by the fact that rat hepatocytes express the polyIg- receptor on their cell surface, whereas guinea pigs (like man) do not. In both rat and guinea pig circulating IgA immune complexes were, to some extent, taken up by Kupffer cells. In vitro, however, IgA failed to increase the antigen uptake to Kupffer cells from either species. On the contrary, IgA actually decreased the antigen uptake by these cells, and therefore appeared functions as an antiopsonin.
Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 1995. , 50 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 474
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-28586Local ID: 13740ISBN: 91-7871-327-7OAI: oai:DiVA.org:liu-28586DiVA: diva2:249397
1995-12-08, Berzeliussalen, Institutionen för Cellbiologi, Hälsouniversitetet, Linköping, 13:00 (Swedish)
Lefvert, Ann Kari, Docent
Papers, included in the Ph.D. thesis, are not registered and included in the posts from 1999 and backwards.2009-10-092009-10-092012-07-16Bibliographically approved