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Am J Physiol. 1997 Apr;272(4 Pt 2):F521-30.

Receptor-mediated endocytosis of immunoglobulin light chains by renal proximal tubule cells.

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Department of Medicine, Tulane University School of Medicine and Veterans Affairs Medical Center, New Orleans, Louisiana 70112, USA.


We examined the binding, endocytosis, and degradation of immunoglobulin light chains by primary cultures from rat renal kidneys and immortalized human proximal tubule cells. Both the association and dissociation of light chain were rapid and plateaued within 30 min at 4 degrees C. Up to 10(-3) M bovine serum albumin did not inhibit light chain binding to cells. Internalization studies with 125I-labeled kappa- and lambda-light chains by cells using the acid wash technique showed that up to 80% of total cell-associated binding at equilibrium (30 min) is rapidly internalized at 22 degrees C. Comparison of binding and internalization of light chains with transferrin, a ligand known to undergo receptor-mediated endocytosis, showed that both ligands displayed saturable kinetics. In contrast, endocytosis of sucrose, a marker for fluid-phase endocytosis, was unsaturable and nearly 200-fold less efficient than light chain internalization. Scatchard analysis of binding experiments done at 4 degrees C with trace 125I-labeled lambda-light chain in presence of 0 to 3.0 x 10(-3) M cold light chain revealed a single class of binding sites with a dissociation constant of 5.0 +/- 0.8 x 10(-5) and a maximal binding capacity of 1.6 +/- 0.3 x 10(-9) mol/mg cell protein. Hypertonic medium, a maneuver which interferes with the formation of the clathrin lattice, reduced endocytosis of light chain significantly but did not affect endocytosis of sucrose. Chloroquine and bafilomycin A, agents that interfere with vesicular acidification, also significantly suppressed light chain endocytosis. Using acid precipitation method, we observed that endocytosis of 125I-labeled lambda-light chain results in degradation by the rat renal proximal tubule cells. Degradation was maximum at 37 degrees C, significantly reduced at 22 degrees C, and absent at 4 degrees C. Excess light chain inhibited degradation of radiolabel, whereas excess albumin had no effect. These studies document the presence of binding sites for light chains on proximal tubule cells that mediate endocytosis of light chains by proximal tubule cells. The present data suggest that receptor-mediated endocytosis of light chains leads to delivery of this ligand to degradative sites through acidified vesicles.

[Indexed for MEDLINE]

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