The involvement of Kupffer cells in the clearance of high molecular weight rat IgA aggregates in rats

Abstract

In the present study the clearance kinetics and tissue distribution of aggregated 125I-labelled monoclonal rat IgA [( 125I] AIgA) of different sizes were studied in rats. Soluble [125I]AIgA disappeared from the circulation in a biphasic manner with an initial rapid distribution half-life (T1) and a second slower half-life (T2). T2 was directly related to the size of the aggregates. High molecular weight [125I]AIgA, containing 10-12 IgA molecules per aggregate [( IgA]10-12), was cleared much faster than low molecular weight aggregates. The main site of clearance was the liver. The larger the size of the AIgA, the more degradation products were found in the circulation. After injection of [IgA]10-12, non-parenchymal cells (NPC) contained three times more radioactivity than parenchymal cells (PC) (NPC:PC ratio 3.06 +/- 0.96). Ratios of 0.82 +/- 0.03 and 0.62 +/- 0.12 were observed when [IgA]5-6 and [IgA]2 were injected respectively, suggesting a greater role for Kupffer cells in the clearance of large-sized IgA aggregates. Kupffer cells were shown to be the main cells for localization of large-sized AIgA established by immunohistochemical staining on liver cryostat sections.