Histamine induces CD86 expression and chemokine production by human immature dendritic cells.
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 1alpha by immature DC and also up-regulates IL-1beta, RANTES, and macrophage-inflammatory protein 1beta but not TNF-alpha 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.
Caron
G
G
Centre d'Immunologie Pierre Fabre, Saint-Julien en Genevois, France.
Delneste
Y
Y
Roelandts
E
E
Duez
C
C
Herbault
N
N
Magistrelli
G
G
Bonnefoy
J Y
JY
Pestel
J
J
Jeannin
P
P
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D017951:Antigen Presentation / Q000187:drug effects; D015703:Antigens, CD / Q000096:biosynthesis*; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis*; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D004306:Dose-Response Relationship, Immunologic; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006632:Histamine / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D039441:Integrin alpha4; D016023:Integrins / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D011969:Receptors, Histamine H1 / Q000502:physiology; D011970:Receptors, Histamine H2 / Q000502:physiology; D015854:Up-Regulation / Q000276:immunology
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D018925:Chemokines; D016207:Cytokines; D006684:HLA-DR Antigens; D016023:Integrins; D008562:Membrane Glycoproteins; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D018799:Intercellular Adhesion Molecule-1; D039441:Integrin alpha4; D006632:Histamine