Abstract
Hyaluronan is made and extruded from cells to form a pericellular or extracellular matrix (ECM) and is present in virtually all tissues in the body. The size and form of hyaluronan present in tissues are indicative of a healthy or inflamed tissue, and the interactions of hyaluronan with immune cells can influence their response. Thus, in order to understand how inflammation is regulated, it is necessary to understand these interactions and their consequences. Although there is a large turnover of hyaluronan in our bodies, the large molecular mass form of hyaluronan predominates in healthy tissues. Upon tissue damage and/or infection, the ECM and hyaluronan are broken down and an inflammatory response ensues. As inflammation is resolved, the ECM is restored, and high molecular mass hyaluronan predominates again. Immune cells encounter hyaluronan in the tissues and lymphoid organs and respond differently to high and low molecular mass forms. Immune cells differ in their ability to bind hyaluronan and this can vary with the cell type and their activation state. For example, peritoneal macrophages do not bind soluble hyaluronan but can be induced to bind after exposure to inflammatory stimuli. Likewise, naïve T cells, which typically express low levels of the hyaluronan receptor, CD44, do not bind hyaluronan until they undergo antigen-stimulated T cell proliferation and upregulate CD44. Despite substantial knowledge of where and when immune cells bind hyaluronan, why immune cells bind hyaluronan remains a major outstanding question. Here, we review what is currently known about the interactions of hyaluronan with immune cells in both healthy and inflamed tissues and discuss how hyaluronan binding by immune cells influences the inflammatory response.
Highlights
The function of our immune cells is to maintain homeostasis
HA TURNOVER DURING HOMEOSTASIS AND INFLAMMATION HA is widely distributed throughout all the tissues in the body with up to 50% being present in the skin
AT HOMEOSTASIS HA as part of the extracellular matrix Hyaluronan is secreted from the cell and forms pericellular or extracellular matrices presumably after cleavage and release from the cell surface
Summary
The function of our immune cells is to maintain homeostasis. When immune cells detect damage or infection, they respond by making an inflammatory response that is aimed at removing the threat. Macrophages are innate immune cells that reside in our tissues and play a key role in maintaining tissue homeostasis Their primary role is to remove dead and damaged cells, and to detect and destroy invading pathogens. Hyaluronan binding by immune cells prevalent in the vitreous of the eye (~100–400 μg/g of wet tissues) and the dermis of the skin (~500 μg/g wet tissue); and present at 10–100 ng/ml in the blood [1, 2]. It is hygroscopic in nature and has viscoelastic properties making it a useful lubricant in joints. Upon the resolution of inflammation, HA production and cellular turnover return to normal and the high molecular mass form predominates again
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