Mast cells: makers AND breakers of allergic inflammation

Role of mast cells in allergy had remained undetermined until the discovery of IgE in 1966. Then, IgE purified from many Liters of plasma, which had been donated from a patient with fatal myeloma, was distributed to researchers all over the world (http://buff.ly/12sD3cO).

From Current Opinion in Allergy and Clinical Immunology:

Mast cells are traditionally viewed only as IgE-activated histamine-providing effector cells of allergic inflammation.



Mast cells. Image source: Wikipedia.

Challenging an old dogma: Mast cell tryptase breaks down IgE, hence breaking the key maker of allergic inflammation.

Mast cells have proinflammatory effects through nonhistamine and non-IgE-mediated routes, e.g platelet-activating factor.

Most surprisingly, mast cells have emerged as modulators and downregulators of allergic inflammation. Mast cells release IL-10.

The seminal work on histamine was published in 1910, but histamine was not identified as a mediator of anaphylactic reactions until 1932. Histamine is a major mediator responsible for the symptoms of allergic rhinitis, with its activities mediated through 4 G protein-coupled receptors. Most of histamine's effects are exerted through the H₁ receptor, but some effects are through the H₂ and H₃ receptors, and possibly also through the H₄ receptor (source: The basics of histamine biology. Lieberman P. Ann Allergy Asthma Immunol. 2011 Feb;106(2 Suppl):S2-5. Epub 2010 Sep 16).

What is Siglec-8 receptor and how it works?

Activation of Siglec-8 causes apoptosis of eosinophils.

Siglec-8 receptor might act as an inhibitor of mast cell degranulation. Sialic acid binding Ig-like lectin 8 (Siglec-8) has also been designated as CD329. Siglec-8 ligation inhibits eosinophil functions. Incubation of eosinophils with Siglec-8 binding monoclonal antibodies under cross-linking conditions caused rapid and profound caspase-dependent apoptosis, and this response could not be rescued by the survival-promoting cytokine interleukin (IL)-5. Activation via Siglec-8 could be used to inhibit eosinophil survival in vivo, providing a novel strategy for reducing or inhibiting these cells in allergic diseases.



Blood cell lineage. Image source: Wikipedia.


Mast cells (mind map).

Mediators released from mast cells

Preformed mediators (from the granules):

- serine proteases, such as tryptase

- histamine (2-5 pg/cell)

- serotonin

- proteoglycans, mainly heparin (active as anticoagulant)

- TNF

Newly formed mediators:

- prostaglandin D2 (PGD2, eicosanoid)

- leukotriene C4 (LTC4, eicosanoid)

- platelet-activating factor (PAF)

- cytokines, e.g. IL-4

- Eosinophil chemotactic factor

References:

Mast cells: makers and breakers of allergic inflammation. Hakim-Rad K, Metz M, Maurer M. Curr Opin Allergy Clin Immunol. 2009 Oct;9(5):427-30.

Mast Cells and Basophils
H(3) receptor antagonist is a new therapeutic strategy for allergic rhinitis, trials are ongoing. JACI, 2012.

Mast Cell Activation Disorders - 2014 free full text review http://buff.ly/1kPDdzo

Mast Cell Disorders (presentation on Google drive):