Binding of α2-macroglobulin to hepatocytes: Mechanism of in vivo clearance

Rat liver sinusoidal endothelial cells (LSECs) express functional low density lipoprotein receptor-related protein-1 (LRP-1)

“…It has been previously reported that the liver PCs are the main site of uptake of  2 M* [10,15]. The authors used autoradiography as a method for identifying the anatomical site of uptake.…”

Altered interaction of Cis-dichlorodiammineplatinum(II)--modified alpha 2-macroglobulin (alpha 2M) with the low density lipoprotein receptor-related protein/alpha 2M receptor but not the alpha 2M signaling receptor.

“…Since ␣ 2 M-proteinase and methylamine derivatives have similar conformations and are recognized equally well by cellular receptors, ␣ 2 M* is often used to designate either receptor recognized form. Exposure of these sites on ␣ 2 M leads to rapid clearance in vivo as demonstrated in mouse, human, and dog circulation and in vitro by cells expressing a cellular receptor for ␣ 2 M* (9,(11)(12)(13)(14). These receptor recognition sites have been localized to a carboxyterminal receptor binding fragment of ␣ 2 M (RBF) ( ‫ف‬ 20,000 M r ) which can be proteolytically derived (15)(16)(17) and has now been cloned and expressed from rat ␣ 1 -macroglobulin (18).…”

Model of alpha 2-macroglobulin structure and function.

“…After reaction with proteinase or amine, a receptorrecognition site is exposed on a2M and the complex is cleared rapidly from the circulation by hepatocytes and reticuloendothelial cells (7)(8)(9). Specific receptors for a2M exist on many cell types, as determined in tissue culture studies (8)(9)(10).…”