title: Histamine induces the generation of monocyte-derived dendritic cells that express CD14 but not CD1a.
abstract: The local cytokine environment and the presence of stimulatory signals determine whether monocytes acquire dendritic cell or macrophage characteristics and functions. In this study, we examined the effect of histamine, a prototypic mediator of allergic inflammation, on the granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4-driven differentiation of monocytes into monocyte-derived dendritic cells (MoDC), which typically showed CD1a+CD14- phenotype. Monocytes from healthy adult donors were cultured with GM-CSF and IL-4 in the presence or absence of histamine, and the phenotypes and function of these cells were analyzed. Histamine induced the generation of CD1a-CD14+ cells, which exhibited cytological and phenotypical characteristics of dendritic cells (DC), showed enhanced phagocytic activity and cytokine-producing capacity, but demonstrated weak allo-stimulatory capacity compared with CD1a+CD14- MoDC. The inhibitory effects of histamine on CD1a+CD14- MoDC differentiation were antagonized by cimetidine, an H2 receptor antagonist, but not by H1 and H3 receptor blockers, and were mimicked by an H2 receptor agonist. Culture supernatant of histamine-treated monocytes also inhibited CD1a+CD14- MoDC differentiation, which was restored by the removal of IL-10. These results suggest that histamine-driven CD1a-CD14+ DC amplify their antigen-independent inflammatory reaction and may contribute to the exacerbation of allergic diseases.
authors.affiliation: Department of Dermatology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan. nkatoh@koto.kpu-m.ac.jp
authors.forename: Norito
authors.initials: N
authors.lastname: Katoh
authors.forename: Fujiko
authors.initials: F
authors.lastname: Soga
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nara
authors.forename: Koji
authors.initials: K
authors.lastname: Masuda
authors.forename: Saburo
authors.initials: S
authors.lastname: Kishimoto
mesh_terms: D018949:Antigens, CD1 / Q000032:analysis*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000032:analysis*; D009000:Monocytes / Q000166:cytology*; D011970:Receptors, Histamine H2 / Q000502:physiology
chemical_list: D018949:Antigens, CD1; C419393:CD1a antigen; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D011970:Receptors, Histamine H2; D015847:Interleukin-4; D006632:Histamine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor