**2. Differentiation and proliferation of mast cells**

## **2.1. Differentiation of mast cells**

Mast cell progenitors are differentiated from pluripotent hematopoietic stem cells in bone marrow. Being different from other granulocytes, mast cells are transported by blood stream to peripheral tissues as mononuclear immature cells without granules in their cytosol [1]. In peripheral tissues, mast cell precursors complete their differentiation and distribution being ready for the host defense (**Figure 2**). According to characters of microenvironment of each peripheral tissue, final types of mature mast cells are altered. In the skin, they differenced into connective tissue‐type mast cells that include heparin proteoglycan and abundant granules in cytosol. Various kinds of proteases and chemical mediators are in granules of connective tissue‐type mast cells by which sever inflammation is induced when they are released at the affected sites. Heparin proteoglycan‐positive mast cells can be detected with not only tolu‐ idine blue but also berberine sulfate and safranin O. In contrast, mast cells that reach to and invade in mucosal tissues differentiate into mucosal‐type mast cells. Mucosal‐type mast cells include chondroitin sulfate as proteoglycan, and cytosolic granules are very few. Chondroitin

**Figure 2.** Origin and transportation of mast cell precursors. Immature mast cells without cytosolic granules are released from bone marrow and distributed to peripheral tissues via circulation. Final maturation of mast cells depends on factors and molecules expressed in microenvironment of each tissue. In the skin (the upper panel), connective tissue‐ type mast cells with rich cytosolic granules are differentiated. In mucosa of the gastrointestinal tract (the lower panel), mucosal‐type mast cells with few cytosolic granules are differentiated.

sulfate‐positive mast cells are identified with alcian blue staining, but not with toluidine blue, berberine sulfate, or safranin O. Connective tissue‐type mast cells are found in the skin and connective tissues in various organs. On the other hand, mucosal‐type mast cells are differen‐ tiated in mucosa of the gastrointestinal tract.
