Clearance of circulating IgA immune complexes is mediated by a specific receptor on Kupffer cells in mice.

Abstract

To characterize the physiology of circulating IgA immune complexes (IgA-IC), the dynamics of IgA-IC removal by the liver were examined. After intravenous injection, covalently cross-linked IgA antibodies to the dinitrophenyl determinant were rapidly removed from the circulation by the liver. Immunofluorescence microscopy and light and electron microscope autoradiography showed that the IgA-IC were associated with Kupffer cells. With increasing doses of injected IgA-IC the clearance velocity approached a maximum, thus prolonging the circulation of IgA-IC. All these observations indicated a receptor-mediated process. Saturating doses of various potential receptor-blocking agents, heat-aggregated mouse IgG, microaggregated human serum albumin, and purified dimeric IgA did not influence the clearance pattern and hepatic uptake of radiolabeled IgA-IC. Mouse livers were also perfused via the portal vein with 1 microgram of IgA-IC. In the presence or absence of serum proteins, 43% of the perfused IgA-IC were removed in a single passage. This liver uptake was not reduced with simultaneous perfusion of large doses of aggregated mouse IgG, aggregated human serum albumin, or purified free dimeric mouse IgA. In contrast, the liver uptake of radiolabeled IgA-IC was decreased by 88% with the addition of 1 mg unlabeled IgA-IC. These observations support the conclusion that removal of IgA-IC from circulation is mediated by a specific IgA receptor on Kupffer cells.

Association of liver cirrhosis related IgA nephropathy with portal hypertension

“…The majority of pIgA is then released back to the circulation in degraded forms [17] . Kupffer cells participate in the removal of IgA expressing specific Fc receptors [18] . PIgA1 is the predominant form in mesangial deposits [19] , yet no antigens have been identified within the mesangial deposits.…”

Role of J Chain and Secretory Component in Receptor‐Mediated Glandular and Hepatic Transport of Immunoglobulins in Man

“…It is possible, therefore, that such cells bear isotype-specific Fc receptors. Fca receptors have been detected on murine Kupffer cells and are thought to be involved in the clearance of [gA-associated immune complexes from the circulation [190]. However, it is not known whether perisinusoidal deposition of IgA in the human liver signifies an initial step in hepatic transport or catabolism of IgA and related immune complexes.…”

Mechanism of transfer of immune complexes from red blood cell CR1 to monocytes

“…lyG was prepared from human serum by precipitation with ammonium sulphate and DEAE ion exchange chromatography, IgG ( Kt mg, ml) was aggregated by heating :tl 63 C for 30 min [18], followed by centrifugalion al 100 000^ for 60 min [ 19] to remove monomer and small aggregates. These aggregates were radiolabelled with ' -M by Ihe iodogen method [20] and opsoni/ed with a 1:10 dilution (final concentralion) of normal htiman serum as a complemenl source for 10 min at 37 C. Immune complexes were immediately cooled lo 4 C and passed over a Sephacryl S-IOOOcoiumn(Pharmacia.…”