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.
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).
References:
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):
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 BasophilsH(3) receptor antagonist is a new therapeutic strategy for allergic rhinitis, trials are ongoing. JACI, 2012.
Mast Cell Disorders (presentation on Google drive):