Cell-cell recognition occurs when complementary molecules on apposing cell surfaces meet. A receptor on one cell surface binds to its ligand on a nearby cell, initiating a cascade of events that regulate cell behaviors ranging from simple adhesion to complex cellular differentiation. Glycans (glycoproteins, glycolipids, proteoglycans) decorate all cell surfaces, and represent the most prominent class of cell surface molecules. Members of this large and varied family are ligands for complementary binding proteins, lectins, on nearby cells.
Lectin-carbohydrate interactions mediate cell-cell interactions throughout the body. The study of cell surface glycans, lectins, and their roles in cell physiology are part of the rapidly expanding field of GLYCOBIOLOGY.
Cell-cell interactions in the nervous system
Neural cells are rich in cell surface glycans called GANGLIOSIDES. Major members of the ganglioside family are ligands for the important cell recognition protein MYELIN-ASSOCIATED GLYCOPROTEIN (MAG). MAG binds to gangliosides on nerve cells to initiate cell-cell recognition that is essential to the stability and health of axons, but MAG also blocks AXON REGENERATION after nervous system injury. Understanding these molecular interactions provides new therapeutic approaches to protect axons and promote nerve regeneration after injury.
Cell-cell interactions in inflammation
Inflammation occurs when circulating white blood cells bind to vascular endothelial cells and invade the underlying tissues. The first step in inflammation is mediated by endothelial lectins called SELECTINS, which bind to glycans on white blood cells. We isolated selectin-binding gangliosides from human neutrophils, the most abundant white blood cells, and determined their structures and functions. Defining endogenous glycans responsible for initiating neutrophil-endothelial interactions may reveal new ways to control inflammation.
In separate studies, a lectin called SIGLEC-8 was discovered on human eosinophils, basophils, and mast cells - the cells that drive allergic inflammation including asthma. Engaging Siglec-8 on the surface of these cells inhibits allergic inflammation. We identified a glycan structure that binds to Siglec-8 and that represents a lead compound for glycan-based asthma therapy. The study of Siglecs as regulators of inflammation may provide therapeutic opportunities to reduce the severity of asthma and other lung inflammatory diseases.
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