Mechanisms for amplified mediator release from colonic mast cells: Implications for intestinal inflammatory diseases

摘要

The mast cell is an enigmatic cell type whose physiological function has preoccupied large numbers of investigators for decades. Some have concluded that the absence of mast cells is incompatible with life, at least in humans, because no human conditions have been documented where these cells are absent from the body. On the other hand, mice harboring specific mutations in certain growth factors, or their receptors, that lead to apparently an almost total ablation of the mast cell lineage, are viable, although they do have several documented abnormalities and may exhibit altered inflammatory responses in a variety of tissues. The viability of such animals may reflect redundancy in the murine system for specific mast cell functions, and/or that other cell types adapt to become repositories of characteristic mast cell mediators. But in any event, mast cells have long been considered to play specific roles in pathophysiology, particularly in disease states that are characterized by allergic inflammation. In the setting of the gastrointestinal tract, release of mast cell mediators has been thought to contribute to tissue injury and inflammation, as well as alterations in epithelial and smooth muscle function, in conditions such as food allergy, systemic anaphylaxis, ulcer disease and inflammatory bowel diseases, as well as, more controversially, irritable bowel syndrome. The spectrum of mast cell involvement has also been expanded by recognition that they can participate in biological events not classically related to allergic responses, such as innate immunity, the phagocytosis of bacteria and cross-talk with the peripheral and enteric nervous systems.