title: Cellular analysis of the histamine H4 receptor in human myeloid cells.
abstract: The human histamine H4 receptor (H4R) is a Gαi/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 Ca(2+) 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.
authors.affiliation: Institute of Pharmaceutical Chemistry/ZAFES, Goethe University Frankfurt, Max-von-Laue Str. 9, D-60438 Frankfurt/Main, Germany. Electronic address: dossantoscapelo@pharmchem.uni-frankfurt.de.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Capelo
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine and Pharmacology, Theodor-Stern-Kai 7, D-60596 Frankfurt/Main, Germany. Electronic address: lehmann@pharmchem.uni-frankfurt.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Lehmann
authors.affiliation: Institute of Pharmaceutical Chemistry/ZAFES, Goethe University Frankfurt, Max-von-Laue Str. 9, D-60438 Frankfurt/Main, Germany. Electronic address: ahmad@pharmchem.uni-frankfurt.de.
authors.forename: Khalil
authors.initials: K
authors.lastname: Ahmad
authors.affiliation: Faculty of Medicine, Institute of Biochemistry I, Goethe-University, Theodor-Stern-Kai 7, D-60596 Frankfurt/Main, Germany. Electronic address: snodgrass@biochem.uni-frankfurt.de.
authors.forename: Ryan
authors.initials: R
authors.lastname: Snodgrass
authors.affiliation: Institute of Pharmaceutical Chemistry/ZAFES, Goethe University Frankfurt, Max-von-Laue Str. 9, D-60438 Frankfurt/Main, Germany. Electronic address: diehl@pharmchem.uni-frankfurt.de.
authors.forename: Olaf
authors.initials: O
authors.lastname: Diehl
authors.affiliation: Faculty of Medicine, Institute of Biochemistry I, Goethe-University, Theodor-Stern-Kai 7, D-60596 Frankfurt/Main, Germany. Electronic address: j.hahn@biochem.uni-frankfurt.de.
authors.forename: Julia
authors.initials: J
authors.lastname: Ringleb
authors.affiliation: Université Laval, Centre de Recherche de l'IUCPQ, 2725 Chemin Sainte-Foy, Québec City, QC G1V 4G5, Canada. Electronic address: nicolas.flamand.1@ulaval.ca.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Flamand
authors.affiliation: Faculty of Medicine, Institute of Biochemistry I, Goethe-University, Theodor-Stern-Kai 7, D-60596 Frankfurt/Main, Germany. Electronic address: weigert@biochem.uni-frankfurt.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Weigert
authors.affiliation: Institute of Pharmaceutical Chemistry, Heinrich-Heine University, Universitaetsstr. 1, D-40225 Düsseldorf, Germany. Electronic address: stark@hhu.de.
authors.forename: Holger
authors.initials: H
authors.lastname: Stark
authors.affiliation: Institute of Pharmaceutical Chemistry/ZAFES, Goethe University Frankfurt, Max-von-Laue Str. 9, D-60438 Frankfurt/Main, Germany. Electronic address: steinhilber@em.uni-frankfurt.de.
authors.forename: Dieter
authors.initials: D
authors.lastname: Steinhilber
authors.affiliation: Institute of Pharmaceutical Chemistry/ZAFES, Goethe University Frankfurt, Max-von-Laue Str. 9, D-60438 Frankfurt/Main, Germany. Electronic address: kahnt@pharmchem.uni-frankfurt.de.
authors.forename: Astrid S
authors.initials: AS
authors.lastname: Kahnt
mesh_terms: D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D016764:Cell Polarity; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism*; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D011968:Receptors, Histamine / Q000235:genetics / Q000378:metabolism*; D011969:Receptors, Histamine H1 / Q000235:genetics / Q000378:metabolism; D011970:Receptors, Histamine H2 / Q000235:genetics / Q000378:metabolism; D000074040:Receptors, Histamine H4; D015054:Zymosan / Q000494:pharmacology
chemical_list: C418607:HRH4 protein, human; D007377:Interleukin-3; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D000074040:Receptors, Histamine H4; D015847:Interleukin-4; D015054:Zymosan; D002118:Calcium
keywords: Eosinophils; Histamine receptor; Inflammation; Macrophages; Monocytes