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By S. Holgate, et. al.

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Histamine, PGD2, tryptase) at sites of early phase responses, as well as the ability of mast-cell-directed therapies such as anti-IgE and cromolyn to block the early phase response provide evidence for the important role of the mast cell in the early phase response. At therapeutic doses antihistamines can inhibit approximately 75% of the skin wheal-and-flare response induced by intradermal allergen, suggesting an important role for histamine in this mast-cell-mediated event. Leukotrienes and EPR and LPR Pretreatment of patients with specific CysLT1-receptor antagonists and LT-biosynthesis inhibitors significantly attenuate allergen-induced early asthmatic responses, as well as partially attenuate late asthmatic responses, providing evidence for a role of CysLTs in the development of allergen-induced responses.

Examples of chemokine receptor expression by circulating cells important to allergic inflammation include: eosinophils and basophils, which express the CC chemokine receptor CCR3, T cells, which express CCR4 and CCR8, and dendritic cells, which express CCR6. CXCR chemokine receptor family Neutrophils express CXCR1 and CXCR2 receptors, which bind IL-8 and this mediates neutrophil tissue recruitment. In addition to the predominant expression of CC chemokine receptors, eosinophils, basophils, and mononuclear cells express the CXC chemokine receptor CXCR4, which is also expressed on neutrophils.

Apart from the consideration of whether either of the studies represents a false negative or positive association, it is important to determine whether the studies truly replicate one another. For example, were they carried out in populations of similar genetic ancestry, or with similar environmental exposures? Were exactly the same polymorphisms studies in the gene and was the phenotype tested the same?  Source: Holloway JW, Yang IA, Holgate ST. Genetics of allergic disease. J Allergy Clin Immunol 2010; 125(2 suppl 2):S81–94.

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