An Acquired and Endogenous Glycocalyx Forms a Bidirectional Don't Eat and Don't Eat Me Barrier to Phagocytosis

Macrophages continuously survey their environment in search of pathogens or apoptotic corpses or debris. Targets intended for clearance expose ligands that initiate their phagocytosis (eat me signals), while others avoid phagocytosis by displaying inhibitory ligands (don't eat me signals). We report that such ligands can be obscured by the glycosaminoglycans and glycoproteins that coat pathogenic as well as malignant phagocytic targets. In addition, a reciprocal barrier of self-synthesized or acquired glycocalyx components on the macrophage surface shrouds phagocytic receptors, curtailing their ability to engage particles. The coating layers of macrophages and their targets hinder phagocytosis by both steric and electrostatic means. Their removal by enzymatic means is shown to markedly enhance phagocytic efficiency. In particular, we show that the removal of mucins, which are overexpressed in cancer cells, facilitates their clearance. These results shed light on the physical barriers that modulate phagocytosis, which have been heretofore underappreciated.

Automated summary

The study reveals the physical barriers that modulate phagocytosis, showing that the coating of glycosaminoglycans and glycoproteins on phagocytic targets, as well as self-synthesized or acquired glycocalyx components on macrophages, hinder phagocytosis by steric and electrostatic means. Enzymatic removal of these barriers significantly enhances phagocytic efficiency, with particular emphasis on the clearance of mucins in cancer cells.