Kupffer cell depletion in vivo results in clearance of large-sized IgA aggregates in rats by liver endothelial cells.
We investigated the clearance kinetics and tissue distribution of different sized IgA in normal and macrophage-depleted rats. Rats were injected iv with liposomes containing dichloromethylene diphosphonate (DMDP). DMDP treatment resulted in complete depletion of liver macrophages 24-48 h after administration. Normal and macrophage depleted rats were injected intravenously with monomeric, dimeric, polymeric or aggregated polymeric IgA (AIgA) and assessed for blood clearance and tissue distribution. In normal rats, clearance of IgA was size dependent, i.e. a faster clearance with increasing size. No differences in clearance kinetics were observed of the different sized IgA between normal and DMDP-treated rats. TCA non-precipitable radioactivity, a measure for degradation of IgA, was found in the circulation of normal and DMDP-treated rats after AIgA administration. The liver was the main organ responsible for the clearance of IgA in normal and DMDP-treated rats. Immunofluorescence studies on liver biopsies indicated that AIgA was associated with Kupffer cells in normal rats. Electron microscopical studies revealed that the AIgA was internalized and located in vesicles in Kupffer cells. In DMDP-treated rats the AIgA was associated with endothelial cells and electron microscopy studies showed that this AIgA was taken up by endothelial cells. These data show that rat liver endothelial cells are able to bind, internalize and degrade AIgA in situations where Kupffer cells are absent, and that these cells may play an important role in the handling of AIgA and IgA-immune complexes.
Bogers
W M
WM
Department of Nephrology, University Hospital Leiden, The Netherlands.
Stad
R K
RK
Janssen
D J
DJ
Prins
F A
FA
van Rooijen
N
N
van Es
L A
LA
Daha
M R
MR
D000470:Alkaloids; D000818:Animals; D000911:Antibodies, Monoclonal; D004002:Clodronic Acid / Q000008:administration & dosage; D004337:Drug Carriers; D004727:Endothelium / Q000378:metabolism* / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D050113:Imino Furanoses; D007070:Immunoglobulin A / Q000493:pharmacokinetics*; D007700:Kinetics; D007728:Kupffer Cells / Q000378:metabolism* / Q000648:ultrastructure; D008081:Liposomes; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008353:Mannitol / Q000031:analogs & derivatives; D011759:Pyrrolidines; D051381:Rats; D011919:Rats, Inbred Strains
D000470:Alkaloids; D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D050113:Imino Furanoses; D007070:Immunoglobulin A; D008081:Liposomes; D011759:Pyrrolidines; D004002:Clodronic Acid; D008353:Mannitol; C043121:2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine