Mechanisms of asthma and allergic inflammationHistamine downregulates monocyte CCL2 production through the histamine H4 receptor
Section snippets
Monocyte enrichment and isolation
Buffy coats from anonymous healthy blood donors obtained from the local blood bank were used. The buffy coats were disposed of by the blood bank after thrombocyte preparation. Total IgE levels, as well as levels IgE against common aeroallergens (sx-1 screening test), were measured (CAP System; Pharmacia, Freiburg, Germany) and were less than the normal limits of 100 kU/L and 0.35 kU/L, respectively. In case of increased IgE levels, the patient was excluded from the study. Human PBMCs were
Expression of the H4R in monocytes
Monocytes have been shown to express the H4R at the mRNA level, as described by us13 and others.6 Here we showed H4R protein expression on monocytes by means of flow cytometry after staining with a selective H4R antibody directed against the C-terminal tail.25 The specificity of the immunoreactivity was controlled by blocking the staining of the H4R antibody with the respective peptide used to generate the antibody (Fig 1, A).
Upregulation of H4R expression by IFN-γ
The regulation of H4R protein expression was investigated after
Discussion
Previously, it has been shown that the H4R has important immunomodulatory effects on human T lymphocytes14, 29 and human DCs13 in vitro. In a recent investigation using a murine model of allergic airway inflammation, an immunomodulatory role for the H4R was also shown in vivo. H4R knockout mice and mice treated with the H4R inhibitor JNJ7777120 had decreased T-lymphocyte function, which was attributed to a decreased cytokine and chemokine production by DCs.15 The monocyte cell fraction that
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Supported by grants from the Deutsche Forschungsgemeinschaft (DFG Gu434/5-1) and SFB 566A6 and Wellcome Trust (United Kingdom).
Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.