Chapter 34 - Regulation and Function of Human Intestinal Mast Cells

Abstract

This chapter provides an overview of the human intestinal mast cells—its regulation and functions. Mast cells exert their effector functions almost exclusively by releasing bioactive molecules, either constitutively or upon stimulation. They help in the release of granule constituents such as histamine, proteases, and proteoglycans. Apart from the release of pre-formed mediators stored in the granules, human intestinal mast cells are capable of releasing de novo synthesized mediators such as leukotrienes and prostaglandins upon activation by ionomycin or IgE receptor cross-linking. Histamine, leukotrienes, and prostaglandin D2 are classical pro-inflammatory mediators released by human intestinal mast cells. Mast cells are also capable of producing cytokines such as turnout necrosis factor-⍺ (TNF-⍺) that play a major role in host defence against bacteria and sepsis. The significance of human mast cells as immunoregulatory cells was recognized by the observation that they can produce a large array of different cytokines, including interleukins, growth factors, and chemokines. Nerve-mast cell interactions have for a long time been suggested to play a role at the gastrointestinal barrier, mostly based on morphological studies indicating a close relationship between mast cells and nerve endings. Regulation of human intestinal mast cell functions include cross-linking of cell surface-bound IgE by antigen or of IgE receptors by anti-IgE receptor antibodies is the only well-defined triggering event leading to degranulation, activation, and mediator release in human intestinal mast cells, regulation of lgE-independent triggering agents, and regulation of mast cell growth factors and modulatory cytokines.