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Cellular analysis of the histamine H4 receptor in human myeloid cells

 
: Capelo, R.; Lehmann, C.; Ahmad, K.; Snodgrass, R.; Diehl, O.; Ringleb, J.; Flamand, N.; Weigert, A.; Stark, H.; Steinhilber, D.; Kahnt, A.S.

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Biochemical pharmacology 103 (2016), pp.74-84
ISSN: 0006-2952
ISSN: 1873-2968
English
Journal Article
Fraunhofer IME ()

Abstract
The human histamine H-4 receptor (H4R) is a G alpha(i/o)-coupled receptor which is mainly expressed on hematopoietic cells. Accordingly, the receptor is implicated in the pathology of various diseases such as autoimmune disorders, bronchial asthma and pruritus. Due to complicated receptor pharmacology, the lack of a reliable antibody and limited availability of primary cells expressing the receptor the physiology of this receptor is still poorly understood. Therefore, we aimed to assess absolute receptor mRNA expression and functionality (intracellular Ca2+ release) in various human myeloid cell types such as granulocytes, monocytes, macrophages and dendritic cells (DCs). This was put into context with the expression of the H1R and H2R. In addition, the influence of various inflammatory stimuli on H4R expression was investigated in macrophages and monocyte-derived DCs. We found that classically activated macrophages treated with pro-inflammatory stimuli down-regulated histamine receptor mRNA expression as did LPS and zymosan A matured monocyte-derived DCs. In contrast, alternatively activated macrophages (IL-4 or IL-13) upregulated H2R and H4R expression compared to controls. Consistent with existing literature, we found eosinophils to be the major source of the H4R. Since availability of primary eosinophils is limited, we developed a cell model based on the differentiated eosinophilic cell line EOL-1, in which H4R pharmacology and physiology may be studied.

: http://publica.fraunhofer.de/documents/N-404412.html