Multiple Receptors Mediate apoJ-Dependent Clearance of Cellular Debris into Nonprofessional Phagocytes

Abstract

Phagocytosis of apoptotic, senescent, and dying cells by macrophages is a well characterized process. More recently it has been shown that in addition to macrophages vital neighboring cells in the affected tissue participate in the cellular clearance. While scavenger receptors have been shown to mediate uptake into macrophages, it is poorly understood how cellular debris is internalized by nonprofessional phagocytes. We here analyze the endocytic activity of vital fibroblasts and epithelial cells exposed to cellular debris and membrane remnants. We show a mutual stimulation in the endocytosis of debris and apolipoproteinJ (clusterin) in these cells. Experiments using RAP (receptor-associated protein) to block ligand binding to LRP and megalin as well as studies in LRP- and megalin-deficient cells suggest that the uptake of apoJ and cellular debris is mediated by megalin, LRP, and yet unidentified internalization mechanisms.