Mastocytosis pathophysiology

Pathophysiology
Mast cells are located in connective tissue, including the skin, the linings of the stomach and intestine, and other sites. They play an important role in helping defend these tissues from disease. By releasing chemical "alarms" such as histamine, mast cells attract other key players of the immune defense system to areas of the body where they are needed.

Mast cells seem to have other roles as well. Because they gather together around wounds, mast cells may play a part in wound healing. For example, the typical itching felt around a healing scab may be caused by histamine released by mast cells. Researchers also think mast cells may have a role in the growth of blood vessels (angiogenesis). No one with too few or no mast cells has been found, which indicates to some scientists that we may not be able to survive with too few mast cells.

Mast cells express a cell surface receptor termed c-kit (CD117), which is the receptor for scf (stem cell factor). In laboratory studies, scf appears to be important for the proliferation of mast cells, and inhibiting the tyrosine kinase receptor with imatinib (see below) may reduce the symptoms of mastocytosis. C-kit mutations (D816V & D816H) are the most common mutations found (80-95%) in mastocytosis. The D816V mutation is located in the catalytic domain of the tyrosine kinase receptor c-Kit occuring in systemic mastocytosis. C-Kit is the receptor for stem cell factor, a key cytokine involved in the generation and differentiation of mast cells from its progenitors; it is encoded by kit, located at 4q12. The presence of the Kit-D816V mutation denotes resistance to imatinib.