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

39 Pages Posted: 22 May 2020 Publication Status: Published

See all articles by Spencer Alexander Freeman

Spencer Alexander Freeman

The Hospital for Sick Children - Program in Cell Biology

Paul R.C. Imbert

Program in Cell Biology, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children

Amra Saric

Neurosciences and Cellular and Structural Biology Division, Eunice Kennedy Shriver National institute of Child Health and Human Development, National Institutes of Health

Kayvon Pedram

Department of Chemistry and Stanford ChEM-H, Stanford University

Carolyn R. Bertozzi

University of California, Berkeley - Department of Chemistry; University of California, Berkeley - Department of Molecular Biology; University of California, Berkeley - Howard Hughes Medical Institute (HHMI); Stanford University - Department of Chemistry

Sergio Grinstein

The Hospital for Sick Children - Program in Cell Biology

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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 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.

Keywords: CD43, syndecan, proteoglycans, sialic acid, mucinase, tumor glycocalyx, efferocytosis, CD47, Dectin-1, Fc receptor

Suggested Citation

Freeman, Spencer Alexander and Imbert, Paul R.C. and Saric, Amra and Pedram, Kayvon and Bertozzi, Carolyn R. and Grinstein, Sergio, An Acquired and Endogenous Glycocalyx Forms a Bidirectional ‘Don't Eat’ and ‘Don't Eat Me’ Barrier to Phagocytosis. Available at SSRN: https://ssrn.com/abstract=3596609 or http://dx.doi.org/10.2139/ssrn.3596609
This version of the paper has not been formally peer reviewed.

Spencer Alexander Freeman (Contact Author)

The Hospital for Sick Children - Program in Cell Biology ( email )

555 University Ave
Toronto, Ontario M5G 1X8
Canada

Paul R.C. Imbert

Program in Cell Biology, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children

555 University Ave
Toronto, Ontario M5G 1X8
Canada

Amra Saric

Neurosciences and Cellular and Structural Biology Division, Eunice Kennedy Shriver National institute of Child Health and Human Development, National Institutes of Health

9000 Rockville Pike
Bethesda, MD 20892
United States

Kayvon Pedram

Department of Chemistry and Stanford ChEM-H, Stanford University

Stanford, CA 94305
United States

Carolyn R. Bertozzi

University of California, Berkeley - Department of Chemistry

310 Barrows Hall
Berkeley, CA 94720
United States

University of California, Berkeley - Department of Molecular Biology

310 Barrows Hall
Berkeley, CA 94720
United States

University of California, Berkeley - Howard Hughes Medical Institute (HHMI)

310 Barrows Hall
Berkeley, CA 94720
United States

Stanford University - Department of Chemistry ( email )

Stanford, CA 94305
United States

Sergio Grinstein

The Hospital for Sick Children - Program in Cell Biology ( email )

555 University Ave
Toronto, Ontario M5G 1X8
Canada

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