Expression and function of histamine receptors 1 and 2 on human monocyte-derived dendritic cells.
BACKGROUND
Histamine is a well-known mediator of inflammatory and allergic reactions and has immunomodulatory capacities. There is increasing evidence that dendritic cells as professional antigen-presenting cells play a major role in the development of allergic reactions. However, a possible link between histamine and dendritic cells has not been investigated thus far.


OBJECTIVE
We investigated the effect of histamine on human monocyte-derived dendritic cells (MoDCs).


METHODS
Expression of histamine H1 and H2 receptors (H1R and H2R) on MoDCs was assessed by means of RT-PCR and flow cytometry. Functional exploration of these receptors was performed by monitoring the increase of intracellular calcium levels (H1R), cyclic adenosine monophosphate formation (H2R), F-actin polymerization, and IL-12p70 production.


RESULTS
MoDCs express both H1R and H2R. Stimulation of dendritic cells with histamine resulted in F-actin polymerization and cyclic adenosine monophosphate production through H2R. Influx of calcium could not be detected after stimulation of dendritic cells with histamine under conditions in which histamine induced calcium influx in monocytes. Histamine and H1R and H2R agonists downregulated IL-12p70 production of prestimulated MoDCs.


CONCLUSIONS
MoDCs express histamine H1 and H2 receptors. Our results indicate chemotactic (F-actin polymerization) and immunomodulatory (inhibition of IL-12p70 production) effects of histamine on MoDCs. Therefore histamine might represent a link between immediate-type hypersensitivity reactions and cellular inflammation in allergic disease (eg, in atopic dermatitis).
Gutzmer
Ralf
R
Department of Dermatology and Allergology, Hannover Medical University, Hannover, Germany.
Langer
Katja
K
Lisewski
Margarete
M
Mommert
Susanne
S
Rieckborn
Dennis
D
Kapp
Alexander
A
Werfel
Thomas
T
D000199:Actins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D009000:Monocytes / Q000166:cytology*; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D011970:Receptors, Histamine H2 / Q000378:metabolism*
D000199:Actins; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D018664:Interleukin-12; D006632:Histamine; D000242:Cyclic AMP; D002118:Calcium