Kupffer cell depletion in vivo results in preferential elimination of IgG aggregates and immune complexes via specific Fc receptors on rat liver endothelial cells.
In the present study we have investigated the clearance kinetics and tissue distribution of monomeric (m) IgG and soluble aggregates of IgG (AIgG) and immune complexes (IC) in normal and Kupffer cell (KC) depleted rats. In normal rats, clearance of mIgG occurred in a biphasic manner with a first half-life (T1/2) (T1) of 36.3 +/- 6.3 min and a second T1/2 (T2) of 168.4 +/- 4.7 min. AIgG composed of 20-27 IgG molecules per aggregate were cleared significantly faster than mIgG with a T1 of 2.5 +/- 0.1 min and a T2 of 32.5 +/- 5.6 min. KC depletion did not have a significant effect on the clearance rate of mIgG (T1: 33.4 +/- 8.9 min; T2; 159.5 +/- 12.5 min), while clearance of AIgG was delayed significantly with T1 4.8 +/- 0.7 min and T2 41.2 +/- 3.2 min. Eight minutes after injection, 77% of AIgG was found in the liver in normal rats while 62% was found in the liver of KC-depleted rats. Double immunofluorescence studies indicated that AIgG in the liver was associated with KC and endothelial cells (EC) in normal rats. In KC-depleted rats, AIgG was strongly associated with EC. A similar staining pattern was observed when IgG-immune IC were administered. The clearance of AIgG in KC-depleted rats was inhibited fully by pre-administration of high concentrations of IgG but not by pretreatment with IgA. asialofetuin (ASFe) or ovalbumin (OVA). Aggregated F(ab')2IgG was cleared with a comparable rate to mIgG from the circulation, again suggesting Fc gamma receptor-mediated elimination of AIgG by EC. There was a reduced degradation of AIgG in rats depleted of KC as compared with normal rats. These data suggest binding and degradation of AIgG by EC in vivo.
Bogers
W M
WM
Department of Nephrology, University Hospital Leiden, The Netherlands.
Stad
R K
RK
Janssen
D J
DJ
van Rooijen
N
N
van Es
L A
LA
Daha
M R
MR
D000818:Animals; D000936:Antigen-Antibody Complex / Q000737:chemistry / Q000493:pharmacokinetics*; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism*; D007728:Kupffer Cells / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility; D014018:Tissue Distribution
D000936:Antigen-Antibody Complex; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010047:Ovalbumin