Histamine H4 receptors modulate dendritic cell migration through skin--immunomodulatory role of histamine.
BACKGROUND
Dendritic cells (DC) are the major antigen-presenting cells and play a key role in adaptive immunity as they are able to activate naive T cells. It was recently described, that the histamine H(4) receptor (H4R) is present on human monocyte-derived DC and that chemotaxis and T-helper (Th)1-Th2 polarization is mediated by this receptor. However, the distribution of histamine receptors on murine DC has not been studied yet.


METHODS
The histamine receptor expression on murine bone marrow (BM)-derived DC and effects of histamine and H4R agonism on DC migration through skin were studied. As it was demonstrated in scratching experiments that NMRI mice are more susceptible to H4R-mediated itch than BALB/c mice, DC function of NMRI and BALB/c mice was compared.


RESULTS
The mRNA of the H1R, H2R and H4R could be detected in murine BM-derived DC, while mRNA of the H3R was found to be low or undetectable. There were no distinct differences in mRNA expression and in H4R protein level (flow cytometry) between NMRI compared with BALB/c mice indicating, that a higher susceptibility is not associated with a generally higher H4R expression in all cell types. Histamine as well as the H4R agonist clobenpropit induced an enhanced chemotaxis in the skin DC migration assay. The enhanced chemotaxis was blocked by the H4R antagonist JNJ7777120. This finding was confirmed by in vitro migration experiments with BM-derived DC.


CONCLUSIONS
Referring to DC migration, blocking the H4R on inflammatory cells might be a promising anti-inflammatory, immunomodulatory strategy.
Bäumer
W
W
Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover Foundation, Hannover, Germany.
Wendorff
S
S
Gutzmer
R
R
Werfel
T
T
Dijkstra
D
D
Chazot
P
P
Stark
H
H
Kietzmann
M
M
D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000378:metabolism / Q000502:physiology*; D054828:Histamine H3 Antagonists / Q000008:administration & dosage; D007093:Imidazoles / Q000008:administration & dosage; D007155:Immunologic Factors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D007271:Injections, Intradermal; D051379:Mice; D008807:Mice, Inbred BALB C; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000502:physiology*; D011968:Receptors, Histamine / Q000502:physiology*; D018100:Receptors, Histamine H3 / Q000378:metabolism; D000074040:Receptors, Histamine H4; D012867:Skin / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013890:Thiourea / Q000008:administration & dosage / Q000031:analogs & derivatives
D054828:Histamine H3 Antagonists; C498829:Hrh4 protein, mouse; D007093:Imidazoles; D007155:Immunologic Factors; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D018100:Receptors, Histamine H3; D000074040:Receptors, Histamine H4; D006632:Histamine; D013890:Thiourea; C086108:clobenpropit