3.1 GLYCOSCIENCE AND HEALTH

Over the past several decades, research from many laboratories has established that glycans are directly involved in normal physiology and in the etiology of every major disease afflicting mankind (Varki et al. 2009). Deciphering the glycome creates an expanding frontier for knowledge and discovery about human health. The section begins with an explanation of the roles of glycans in fundamental biological processes, such as inflammation and immune system activation, and moves on to consider examples from infectious diseases and vaccine development. It then turns to chronic diseases such as diabetes and cardiovascular disease and to a discussion of cancer and congenital genetic disorders. Finally, the significance of glycans in the development of new pharmaceuticals is discussed. Examples of the diverse roles that glycans play in human health are provided to illustrate the breadth and importance of glycoscience to this field. The section does not attempt to comprehensively address all glycan functions. As it illustrates, however, the development of a more complete understanding of glycans can impact the diagnosis and treatment of infectious, chronic, and genetic diseases. (See Figure 3-1 for a partial summary of some of the roles played by glycans in biological systems.)

3.1.1 Glycans’ Regulation of Inflammation

Inflammation, both chronic and acute, underlies the pathology of a broad range of diseases, including diabetes, cancer, arthritis, asthma, heart disease, and infectious disease (Barreiro and Sanchez-Madrid 2009; Celie et al. 2009; Kobayashi et al. 2009a; Korpos et al. 2009; Langer and Chavakis 2009; Schauer 2009; Sperandio et al. 2009; McEver 2010; McEver and Zhu 2010; Sorokin 2010; Zarbock et al. 2011). Glycans play a key role in inflammation at many levels.

Inflammation begins with the generation of multiple cytokines by various cell types that react to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) arising from damaged tissues. Many of these molecular patterns are glycoconjugates, and many cytokines themselves bind to endogenous glycans. More recently recognized is the fact that glycans found in an individual host, such as a human, can serve as self-associated molecular patterns (SAMPs) that dampen inflammation and that SAMPs can be mimicked by microbes (mSAMPs; Varki 2011). The signaling associated with these molecular patterns is part of the multistep process that results in leukocyte homing into affected tissues, a process initiated when leukocytes adhere to activated endothelial cells lining blood vessel walls. This Velcro-like adhesion slows the rapidly flowing leukocytes, causing them to roll along the surfaces of the endothelial cells. Rolling leukocytes are



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