Kupffer cell depletion in vivo results in clearance of large-sized IgA aggregates in rats by liver endothelial cells

Abstract

SUMMARYWe 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 maerophage depleted rats were injected intravenously with monomeric, dimeric. polymeric or aggregated polymeric IgA (AlgA) 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 differenees in clearance kinclics were observed ofthe different sized IgA between normal and DMDP-lreated rats. TCA non-precipitable radioactivity, a measure for degradation of IgA, was found in the circulation of normal and DMDP-treated rats after AlgA administration. The liver was the main organ responsible for the clearance of IgA in normal and DMDP-trcated rats. Immunofiuorescence studies on liver biopsies indicated thai AlgA was associated with Kupffer cells in normal rats. Electronmicroscopical studies revealed that the AlgA was internalized and located in vesicles in Kupffer cells. In DMDP-lreated rats the AlgA was associated with endothelial cells and electron microscopy studies showed that this AlgA was taken up by endothelial cells. These data show that rat liver endothelial cells are able to bind, internalize and degrade AlgA in situations where K upffer cells are absent, and that these cells may play an important role in the handling of AlgA and IgA-immune complexes.

Kupffer cell depletionin vivoresults in preferential elimination of IgG aggregates and immune complexes via specific Fc receptors on rat liver endothelial cells

“…No differences in the number of KC per 100 nucleated liver cells were observed (Bogers et al, 1991).…”

“…To find out whether repopulaton of KC Fig. 1 in the liver resulted in reversal of the rate of clearance of AIgG, four rats were first depleted of KC, and on day 5 when the number of KC had returned to 50% of the original value (Bogers et al, 1991), assessed for clearance of AIgG. In these rats the delayed clearance of AIgG was restored to normal (T 1: 3-4 + 0 5 min; T2: 35-7+8 0 min, P>0-1 as compared to normal rats).…”

“…Rats were injected intravenously with 0 5 ml (containing about 5 mg of liposome entrapped CL2MDP) liposome suspension. After 24-48 h clearance and tissue distribution, studies were performed because no KC were present during this period (Van Rooijen et al, 1990;Bogers et al, 1991).…”

“…IgG preparations were aliquoted and stored at -70 C. Radioiodination For clearance and tissue distribution studies, IgG was radiolabelled with 1251 (Na'251, Radiochemical Centre, Amersham. UK), in the presence of lodogen (1,3,4,6-tetrachloro3x,6x-diphenyl glycol uril, Pierce Chemical Co., Rockford, IL) as described previously (Bogers et al, 1991).…”

“…Recently a method was developed to specifically eliminate KC in vivo by using drugs encapsulated in liposomes (Van Rooijen & Claassen, 1988). With this method, rodents can be fully depleted of liver and spleen macrophages without damaging other cell types (Van Rooijen & Claassen, 1988;Van Rooijen, 1989;Van Rooijen et al, 1990;Bogers et al, 1991). Using this approach, we have investigated the contribution of liver EC and KC in the clearance and handling of IgG aggregates and IgG-IC.…”