Biology and Chemistry of Beta Glucan Vol: 1 Beta Glucans - Mechanisms of Action

Full text available.

β-Glucans are well-established and powerful immunomodulators. Their history, however, has been complicated and is full of dead ends. Starting from their chemical composition and structure, continuing with their biological effects and activities, and ending with the mechanism of their function, β-glucans are extensively studied for over 70 years. This Chapter is focused on the history of β-glucans, going back to the half of the 19th century, when β-glucan was believed to be a type of cellulose, and to the 40s of the last century when Shear and Turner described a polysaccharide substance, isolated from Serratia marcescens, that caused necrosis of tumors.

β-Glucan is a well-known biological response modifier (BRM) that has been used as an adjuvant therapy for cancer since 1980, primarily in Japan. It represents a class of fungal cell wall polysaccharides that are made up entirely of glucose that is β(1-3)-linked together in linear chains with a variable frequency of β(1-6)-linked side chains. β-glucans from cereal grains such as oats or barley can have a similar BRM activity in tumor models but contain linear chains with β(1-4)-linkages in addition to β(1-3)-linkages. β-Glucans also enhance the innate host defense against certain bacteria, yeast, and viral pathogens. In the 1990s, there were attempts in the U.S. to develop a yeast β-glucan as an anti-infective BRM. In addition, β-glucans are also considered to be important in prophylaxis against irradiation. In summary, β-glucan might be the most in important natural immunomodulator.

β-Glucans are naturally occurring carbohydrates found in plants, fungi and some bacterial species. They possess immunomodulating activities, but their mechanisms of action are not well understood. β-Glucans are recognised by the vertebrate immune system via pattern recognition receptors such as Dectin-1. Recent studies of Dectin-1 and other β-glucan receptors have enabled us to begin to unravel the mechanisms underlying the immune stimulating properties of these carbohydrates. There is also a strong evidence that β-glucan recognition is an important component of anti-fungal immunity. Here we will review the mammalian β-glucan receptors, with a particular focus on Dectin-1.

The beneficial properties of β-glucan in cancer therapy have been recognized for centuries. Their proposed mechanism of action occurs mainly via stimulation of macrophages and priming of neutrophil complement receptor 3 (CR3) for eliciting CR3-dependent cellular cytotoxicity of iC3b-opsonized tumor cells. Recent studies revealed that β-glucans may also promote anti-tumor T cell responses. Thus, β-glucan-mediated tumor immunotherapy may engage both the innate and adaptive anti-tumor immune reponses to restrain tumor progression. In this Chapter, we will describe the mechanism of action of β-glucan in cancer immunotherapy and discuss the available data from current β-glucan clinical trials. The potential challenges for this therapy will be also discussed. It is proposed that a biological response modifer β-glucan can serve as a potent adjuvant to specifically modulate both the innate and adaptive immune cells.

β(1-3)-D-Glucans are a structurally varied class of polysaccharides that have been long studied for their immunomodulatory and physical properties. In this review we focus on the work intersecting these two properties, the use of β(1-3)-D-glucans for drug delivery. Natural and chemically-modified β(1-3)-D-glucans have been used for drug delivery in many forms: 1) release of drugs from a glucan gel matrix, 2) in combination with other materials to form suitable drug delivery systems, 3) as carriers in drug formulations consisting of gels, tablets and ingestible films, 4) as soluble and particulate conjugates, and 5) and as soluble and particulate β(1-3)- D-glucans for encapsulation and delivery of macromolecules. The scope of this review is to summarize the significant developments using soluble and insoluble β(1-3)-D-glucans for drug delivery reported in the literature.

Beta-glucans (BG) are major cell wall components of fungi and are also found in plants and some bacteria. BG are a heterogeneous group of polymers, consisting of β(1-3) linked and β(1-6) linked β-Dglucopyranosyl units. As they are not found in animals, BG are considered to have pathogen-associated molecular patterns (PAMPs) and are recognized by the innate and acquired immune systems. BG show various activities, both beneficial and detrimental to the host. This chapter focuses on the detrimental effects of BG. It was found that BG induced inflammation, sepsis, and rheumatoid arthritis. BG also have the characteristics of an antigen, strongly supporting BG as representative PAMPs from fungi.

Full text available.