Mast cell and atopy

During the first 100 years after Paul Ehrlich discovered them, mast cells were believed to be a component of connective tissue that was derived from undifferentiated mesenchymal cells. However, Kitamura and co-workers demonstrated that mast cells (MCs) arise from multipotent hematopoietic progenitors in bone marrow. These cells took their name from the Greek word mastzellen, meaning well-fed as Paul observed the granular nature of the cells. MCs are usually perivascular. They are generally noted to be particularly abundant in tissues that are exposed to the environment. Committed MC progenitors are rare in bone marrow suggesting they are rapidly released into the blood where they circulate and move out into the peripheral tissues. This migration is controlled in a tissue specific manner. Basal trafficking to the intestine or the lung requires expression of α4β7 integrin and the chemokine receptor CXCR2 by the MC progenitors and expression of VCAM-1 in the intestinal and pulmonary endothelium. In humans, MCs have been described to reach densities of up to 500 to 4,000 per mm3 in the lungs, 7,000 to 12,000 per mm3 in skin and 20,000 per mm3 in the gastrointestinal tract. These densities have been noted to increase in the skin of humans that is not covered by clothing, suggesting that regions that experience continual environmental exposure respond by either recruiting more MCs or inducing their local proliferation. Since their discovery in 1878, MCs have primarily been regarded as effector cells promoting harmful IgE mediated allergic reactions following secondary exposure to allergens. However, in the last decade they were being increasingly recognized for their key role in pathogen recognition, and in initiating primary protective innate and adaptive immune responses. To function as immune surveillance cells, MCs must be able to interact with incoming pathogens. MC activation usually occurs through at least 3 mechanisms of pathogen recognition: (i) direct binding of pathogens or their components by pathogen associated molecular pattern (PAMP) receptors located on the MC surface; (ii) binding of opsonized bacteria or their products by complement receptors or immunoglobulin receptors, or (iii) recognition of endogenous peptides produced by infected or injured host cells. One class of PAMP receptors are the Toll like receptors (TLRs). Each TLR binds a specific component of different pathogens. Human MCs have been shown to express TLR-1,-2,-3,-4,- 5,-6,-7 and -9 under certain conditions.