Kupffer Cell Depletion in Vivo Results in Preferential Elimination of IgG Aggregates and Immune Complexes Via Specific Fc Receptors on Rat Liver Endothelial Cells

Overview

Journal Clin Exp Immunol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 1991 Nov 1

PMID 1934600

Citations 12

Authors

W M Bogers

R K Stad

D J Janssen

N van Rooijen

L A van Es

M R Daha

Affiliations

Soon will be listed here.

Abstract

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.

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References

Bogers W, Gorter A, Janssen D, Rits M, Bazin H, van Es L . The involvement of Kupffer cells in the clearance of high molecular weight rat IgA aggregates in rats. Scand J Immunol. 1990; 31(6):679-89. DOI: 10.1111/j.1365-3083.1990.tb02819.x. View

van Rooijen N . The liposome-mediated macrophage 'suicide' technique. J Immunol Methods. 1989; 124(1):1-6. DOI: 10.1016/0022-1759(89)90178-6. View

Tax W, van de Winkel J . Human Fc gamma receptor II: a standby receptor activated by proteolysis?. Immunol Today. 1990; 11(9):308-10. DOI: 10.1016/0167-5699(90)90125-s. View

Bogers W, Stad R, Janssen D, Prins F, van Rooijen N, van Es L . Kupffer cell depletion in vivo results in clearance of large-sized IgA aggregates in rats by liver endothelial cells. Clin Exp Immunol. 1991; 85(1):128-36. PMC: 1535711. DOI: 10.1111/j.1365-2249.1991.tb05693.x. View

Benacerraf B, Sebestyen M, Cooper N . The clearance of antigen antibody complexes from the blood by the reticuloendothelial system. J Immunol. 1959; 82(2):131-7. View

Knutson D, Kijlstra A, van Es L . Association and dissociation of aggregated IgG from rat peritoneal macrophages. J Exp Med. 1977; 145(5):1368-81. PMC: 2180672. DOI: 10.1084/jem.145.5.1368. View

Kijlstra A, Knutson D, Van der Lelij A, van Es L . Characteristics of soluble immune complexes prepared from oligovalent DNP conjugates and anti-DNP antibodies. J Immunol Methods. 1977; 17(3-4):263-77. DOI: 10.1016/0022-1759(77)90109-0. View

Kijlstra A, van Es L, Daha M . Enhanced degradation of soluble immunoglobulin aggregates by macrophages in the presence of complement. Immunology. 1979; 37(3):673-80. PMC: 1457712. View

Ryan U, Schultz D, Del Vecchio P, Ryan J . Endothelial cells of bovine pulmonary artery lack receptors for C3b and for the Fc portion of immunoglobulin G. Science. 1980; 208(4445):748-9. DOI: 10.1126/science.7367890. View

10.

Shingu M, Hashimoto Y, Johnson A, Hurd E . The search for Fc receptors on human tissues and human endothelial cells in culture. Proc Soc Exp Biol Med. 1981; 167(2):147-55. DOI: 10.3181/00379727-167-41140. View

11.

Pulford K, Souhami R . The surface properties and antigen-presenting function of hepatic non-parenchymal cells. Clin Exp Immunol. 1981; 46(3):581-8. PMC: 1536307. View

12.

Rifai A, Mannik M . Clearance of circulating IgA immune complexes is mediated by a specific receptor on Kupffer cells in mice. J Exp Med. 1984; 160(1):125-37. PMC: 2187430. DOI: 10.1084/jem.160.1.125. View

13.

Dijkstra C, Dopp E, Joling P, Kraal G . The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology. 1985; 54(3):589-99. PMC: 1453512. View

14.

Skogh T, Blomhoff R, Eskild W, Berg T . Hepatic uptake of circulating IgG immune complexes. Immunology. 1985; 55(4):585-94. PMC: 1453780. View

15.

Harms G, HOEDEMAEKER P, HARDONK M . A histochemical study about the involvement of rat liver cells in the uptake of heterologous immune complexes from the circulation. Histochemistry. 1985; 82(5):477-82. DOI: 10.1007/BF02450483. View

16.

Veerhuis R, van Es L, Daha M . In vivo modulation of rat complement activities by infusion of anti-H antibodies. Immunobiology. 1985; 170(3):133-45. DOI: 10.1016/S0171-2985(85)80086-3. View

17.

Harms G, Atmosoerodjo J, Meijer D, HARDONK M, HOEDEMAEKER P . Studies on the mechanism of binding and uptake of immune complexes by various cell types of rat liver in vivo. Scand J Immunol. 1986; 23(1):127-33. DOI: 10.1111/j.1365-3083.1986.tb01950.x. View

18.

Harms G, HOEDEMAEKER P, HARDONK M . Hepatic uptake of autologous immune complexes in the rat. Scand J Immunol. 1986; 23(4):441-7. View

19.

Steffan A, Gendrault J, McCuskey R, McCuskey P, KIRN A . Phagocytosis, an unrecognized property of murine endothelial liver cells. Hepatology. 1986; 6(5):830-6. DOI: 10.1002/hep.1840060505. View

20.

Lobatto S, Daha M, Voetman A, van Es A, Pauwels E, van Es L . Clearance of soluble aggregates of human immunoglobulin G in healthy volunteers and chimpanzees. Clin Exp Immunol. 1987; 69(1):133-41. PMC: 1542252. View