2. Academic Validation
  3. An Acquired and Endogenous Glycocalyx Forms a Bidirectional "Don't Eat" and "Don't Eat Me" Barrier to Phagocytosis

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

  • Curr Biol. 2021 Jan 11;31(1):77-89.e5. doi: 10.1016/j.cub.2020.09.082.
Paul R C Imbert 1,  Amra Saric 2,  Kayvon Pedram 3,  Carolyn R Bertozzi 4,  Sergio Grinstein 5,  Spencer A Freeman 6
Affiliations

Affiliations

  • 1 Program in Cell Biology, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, 686 Bay Street, 19-9800, Toronto, ON M5G 0A4, Canada.
  • 2 Neurosciences and Cellular and Structural Biology Division, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
  • 3 Department of Chemistry and Stanford ChEM-H, Stanford University, Stanford, CA 94305, USA.
  • 4 Department of Chemistry and Stanford ChEM-H, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford, CA 94305, USA.
  • 5 Program in Cell Biology, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, 686 Bay Street, 19-9800, Toronto, ON M5G 0A4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada; Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON M5B 1W8, Canada. Electronic address: sergio.grinstein@sickkids.ca.
  • 6 Program in Cell Biology, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, 686 Bay Street, 19-9800, Toronto, ON M5G 0A4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada. Electronic address: spencer.freeman@sickkids.ca.
PMID: 33096038 DOI: 10.1016/j.cub.2020.09.082
Abstract

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. VIDEO ABSTRACT.

Keywords

CD47; Candida albicans; hyaluronan; mucinase; sialic acid; surface charge; syndecan; synovial-resident macrophages; tumor-associated macrophages.

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