Histamine Induces CD86 Expression and Chemokine Production by Human Immature Dendritic Cells

Abstract

Mast cells and immature dendritic cells (DC) are in close contact in peripheral tissues. Upon activation, mast cells release histamine, a mediator involved in the immediate hypersensitivity reaction. We therefore tested whether histamine could affect human DC activation and maturation. Histamine induces CD86 expression on immature DC in a dose-dependent (significant at 10−7 M) and transient manner (maximal after 24-h stimulation). Histamine also transiently up-regulates the expression of the costimulatory and accessory molecules, CD40, CD49d, CD54, CD80, and MHC class II. As a consequence, immature DC exposed for 24 h to histamine stimulate memory T cells more efficiently than untreated DC. In addition, histamine induces a potent production of IL-6, IL-8, monocyte chemoattractant protein 1, and macrophage-inflammatory protein 1α by immature DC and also up-regulates IL-1β, RANTES, and macrophage-inflammatory protein 1β but not TNF-α and IL-12 mRNA expression. Histamine activates immature DC through both the H1 and H2 receptors. However, histamine-treated DC do not have a phenotype of fully mature cells, as they do neither show significant changes in the expression of the chemokine receptors, CCR5, CCR7 and CXC chemokine receptor 4, nor expression of CD83 de novo. These data demonstrate that histamine activates immature DC and induces chemokine production, thereby suggesting that histamine, via stimulation of resident DC, may participate locally in T cell stimulation and in the late inflammatory reaction associated with allergic disorders.

IgE-Mediated Mast Cell Activation Induces Langerhans Cell Migration In Vivo

“…However, there was a slight trend toward reduced LC numbers in the activated LNs, which may reflect some cross-inhibition of H2 receptors by the relatively high doses of pyrilamine used in this study. Histamine up-regulates the expression of CD86, CD40, CD54, CD80, and MHC class II, as well as induces proinflammatory cytokine and chemokine production by human immature dendritic cells through H1 and H2 receptors (11). However, histamine alone does not up-regulate CCR7, which is thought to be crucial for dendritic cell migration and can be regulated by IL-1␤ or TNF (40,41).…”

“…A recent report has also demonstrated that mast cell-derived TNF is primarily responsible for LN swelling following bacterial or compound 48/80-induced mast cell activation (20), while histamine did not contribute significantly to this response. Dendritic cells have, however, been shown to express H1, H2, and H3 receptors and to undergo significant maturational changes as a result of histamine treatment (11,(21)(22)(23).…”

“…They express high-affinity Fc⑀RI and IgE-mediated activation leads to the release of multiple preformed, newly formed, and lipid mediators. Preformed mediators, include histamine and granule-associated TNF, which induce dendritic cell maturation (11,12). Mast cells produce a number of cytokines in the hours following IgE-mediated activation with known effects on dendritic cells including TNF, IL-1␤, and GM-CSF (13)(14)(15).…”

Histamine H4 Receptor Stimulation Suppresses IL-12p70 Production and Mediates Chemotaxis in Human Monocyte-Derived Dendritic Cells

“…The expression of H1R and H2R on human monocyte-derived DC (MoDC) has also recently been reported (10 -13), and stimulation of MoDC with histamine resulted in induction of CD86 surface expression (14), suppression of IL-12 production (10 -13), and polarization of DC into Th2 cell promoting cells (10,13).…”

The Involvement of Cholesterol in Sepsis and Tolerance to Lipopolysaccharide Highlighted by the Transcriptome Analysis of Zebrafish (Danio rerio)

“…There were also some modulated genes with important anti-inflammatory properties in 6-dpf fish: the histamine receptor H2 (HRH2), that acts as a suppressor of antigen presentation capacity and enhances IL10 production [58][59][60][61][62][63] and the toll IL1 receptor domain-containing adaptor (SARM1) that down-modulates NFKB and IRF3-mediated TLR3 and TLR4 signaling. 64 Similar to the LD treatment, some proteins related to tissue damage and apoptosis were also modulated in zebrafish in response to the SLD treatment, but the inflammatory effects did not seem to be as apparent as for the lethal treatment.…”