Effects of atopy and grass pollen season on histamine H4 receptor expression in human leukocytes

Background: The histamine H-4 receptor (H4R) is a novel therapeutic target to treat allergic inflammation. Objective: To profile messenger RNA (mRNA) expression of H4R isoforms in human cells and evaluate the effects of atopy and grass pollen season on H4R expression in peripheral blood leukocytes ex vivo. Methods: H4R isoform expression was assayed by quantitative polymerase chain reaction in human airway and peripheral RNA. During low and high grass pollen seasons, leukocytes were isolated from venous blood and fractionated into peripheral blood mononuclear cells and polymorphonuclear cells (PMN). H4R expression was determined and related to atopy, defined by a level of specific IgE to Timothy grass pollen of >= 0.35 kU(A)/L (n = 7 atopic patients and 9 controls). Results: Expression of total and full length H4R was at the limit of detection but predominant in peripheral blood leukocytes, where truncated H4R was expressed exclusively (<= 300-fold less). Suggestive evidence for total H4R in airway cells and brain indicated an expression <= 260-fold lower than in peripheral blood mononuclear cells. Total H4R mRNA expressionwas unaffected by atopy or grass pollen season, but truncated H4R was significantly reduced during high grass pollen season in total leukocytes, independently of atopy (P < .01). Conclusion: H4R mRNA is predominantly expressed in peripheral blood leukocytes, and total H4R expression levels are unrelated to atopy or grass pollen season. Atopy-independent seasonal variation in truncated H4R expression might affect putative negative regulation of full length H4R during high grass pollen season. If verified, this should be considered during the design of drugs targeting H4R to treat allergic inflammation, particularly for seasonal allergic rhinitis. (C) 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.