[Frontiers in Bioscience 17, 430-437, January 1, 2012]

H4 receptors in mast cells and basophils: a new therapeutic target for allergy?

Bernhard F. Gibbs1, Francesca Levi-Schaffer2

1Medway School of Pharmacy, University of Kent, Chatham Maritime, United Kingdom, 2Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel


1. Abstract
2. Role of mast cells and basophils in allergic inflammation
2.1. Mast cells and basophils as a major source of histamine in humans
2.2. Differential expression and function of histamine receptors in mast cells and basophils
2.3. Therapeutic potential of modulating H4-receptor function
3. Acknowledgements
4. References


It has long been recognised that mast cells and basophils are prominent sources of preformed histamine in humans and that this biogenic amine serves as one of the most important inflammatory mediators. In allergic diseases, histamine has previously been shown to partially modulate symptoms such as airway obstruction, mucus secretion, reddening of the skin and itch, all of which were attributed to engagement of H1-receptors with the amine. However, more recently it has been shown that certain key biological functions of histamine, such as itch, are also crucially controlled by H4-receptor stimulation, resulting in a growing interest in combinational anti-H1 and -H4 therapeutic approaches. Moreover, research is beginning to shed light on a role of H4-receptors in mast cell precursor trafficking to various tissues commonly affected by allergic inflammation. Furthermore, H4-receptors are also expressed on mature basophils and other effector cells of allergic reactions, such as eosinophils. This presents exciting possibilities in terms of potentially modulating the pro-allergic function of these cells as well as