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Updated: Aug 10, 2026
Characterization of Human Monocyte Subsets by Whole Blood Flow Cytometry Analysis
Published on: October 17, 2018
Histamine downregulates CD14 expression via H2 receptors on human monocytes
Hideo Kohka Takahashi1, Toshihiko Morichika, Hiromi Iwagaki
1Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, 700-8558 Okayama, Japan.
Abstract:
Lipopolysaccharide (LPS) binds to LPS-binding protein (LBP) in plasma and is delivered to the cell surface receptor CD14 on human monocyte. LPS is transferred to the transmembrane signaling receptor toll-like receptor (TLR) 4. In the present study, the effect of histamine on the expression of CD14 on human monocytes was investigated. Histamine concentration- and time-dependently decreased the expression of cell surface CD14, whereas histamine did not decrease mRNA for CD14 nor increase soluble CD14 (sCD14). The inhibitory effects of histamine on CD14 expression were antagonized by H2-receptor antagonist, but not by H1 and H3/H4 antagonist. The effects of selective H2-receptor agonists, 4-methylhistamine and dimaprit, on CD14 expression mimicked that of histamine indicating that histamine regulated CD14 expression through the stimulation of H2-receptors. The pretreatment with histamine partially inhibited the LPS-induced TNF-alpha production in human peripheral blood mononuclear cells (PBMC). Such inhibition might be due to the down-regulation of CD14 expression on monocytes by histamine.
Insights
Histamine reduces CD14 expression on monocytes via H2-receptors, potentially inhibiting lipopolysaccharide (LPS)-induced responses. This finding offers insights into immune modulation by histamine.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Lipopolysaccharide (LPS) initiates inflammatory responses by binding to CD14 and Toll-like receptor 4 (TLR4) on monocytes.
- CD14 is a crucial cell surface receptor for LPS recognition and subsequent immune activation.
Purpose of the Study:
- To investigate the effect of histamine on the expression of CD14 on human monocytes.
- To elucidate the receptor pathways involved in histamine's modulation of CD14 expression.
Main Methods:
- Human peripheral blood mononuclear cells (PBMC) were treated with histamine.
- Flow cytometry was used to assess cell surface CD14 expression.
- Quantitative real-time PCR (qRT-PCR) was employed to measure CD14 mRNA levels.
- Experiments involved H2-receptor antagonists and agonists.
Main Results:
- Histamine significantly decreased cell surface CD14 expression in a concentration- and time-dependent manner.
- Histamine did not affect CD14 mRNA levels or soluble CD14 (sCD14) concentrations.
- The inhibitory effect of histamine on CD14 expression was specifically antagonized by H2-receptor antagonists.
- H2-receptor agonists mimicked histamine's effect on CD14 expression.
- Histamine pretreatment partially inhibited LPS-induced TNF-alpha production in PBMC.
Conclusions:
- Histamine down-regulates CD14 expression on human monocytes through the stimulation of H2-receptors.
- This histamine-mediated reduction in CD14 may contribute to the inhibition of LPS-induced inflammatory responses.
