Mast cell secretory system

Mast cells (MCs), the term coined by Ehrlich (1876) for highly granular cells with a propensity for basic stains such as toluidine blue, are able to store inflammatory mediators in secretory granules. Mediator release occurs in response to a variety of stimuli, the best characterised of which involves antigenic stimulation via high affinity receptor for IgE (FcεRI).

Three different types of mediators have been described in MCs:
1. Pre-formed and stored mediators, such as histamine, serotonin and tryptase.
2. Newly synthesised mediators, such as interleukins and cytokines, IFNs, TNF-, IL3 and IL4.
3. Lipid mediators, such as PGD2, PGE2, LTB4, LTC4 and PAF.

Mast cell mediators play an important role in cell-cell interactions and their cross-talk with other cells such as B and T cells and macrophages. Some of these mediators are able to impose a self-regulatory effect on MC for regulated-expression of co-stimulatory molecules, and this mechanism increases the efficacy of mast cells in T cell activation (Sayed and Brown 2007). These interactions are important mechanisms to stimulate primary and secondary immuneresponses against pathogens. In addition to T cells stimulators, MCs can produce several products that can promote dendritic cells (DC) to undergo migration and maturation (Marshall 2004; Galli, Nakae et al. 2005).

Mast cell mediators also contribute in their pathogenesis in MCs-related diseases. For example, tryptase, chymase, IL-4 and IL-13 have been demonstrated to have a range of actions consistent with key roles in inflammation, tissue remodelling, and bronchial hyperresponsiveness, that are observed in allergic asthma (Hart 2001).

In recent years, the secretory system in MCs and some other hematopoietic cells has increasingly attracted the attention of cell biologist as a paradigm for a unique machinery of regulated secretion (Griffiths 1996). The general idea concerning the origin of secretory granules is that they are budding from the Golgi apparatus. Protein mediators are synthesised on ribosomes and transferred to endoplasmic reticulum and from there to Golgi organelles, where they are stored in the secretory granules following a variety of post-translational modifications. Cell stimulation via membrane receptors is the common mechanism for the fusion of secretory granules with the cytoplasmic membrane, which initiates release of mediators.

Mast cells contain acidic, enzyme-containing intracellular compartments, called lysosomes, which derive from endocytic vesicles and form part of the digestive system of cell. For many years, lysosomes were considered to be the final point of endocytic process. However, new data about secretory mechanism of mast cells suggest the existence of a new kind of lysosomes, called secretory lysosomes (Stinchcombe and Griffiths 1999). This regulated secretory system has been reported not only for mast cells, but also for some other hematopoetic cells, such as neutrophils, basophils, T and B cells, platelets and some other non-hematopoetics cells, such as melanocytes (Stinchcombe and Griffiths 1999).