Differentiation of monocytes into macrophages induces the upregulation of histamine H1 receptor.
BACKGROUND
Histamine modulates several functions in human monocytes, macrophages, and dendritic cells. However, responses elicited by histamine differ depending on cell type, suggesting variable expression of histamine receptors in the monocyte/macrophage lineage.


OBJECTIVE
We sought to examine whether the expression of H(1) receptors was regulated by cell differentiation of human monocytes into macrophages or dendritic cells.


METHODS
Expression of H(1) receptor was evaluated by RT-PCR and western blot in monocytes, monocyte-derived macrophages (MDMs), monocyte-derived dendritic cells (DCs) and human lung macrophages (HLMs).


RESULTS
Expression of H(1) receptor mRNA and protein was higher in HLMs and DCs than in monocytes. H(1) expression was approximately 15-fold and 4-fold higher in MDMs and HLMs, respectively, as compared with that seen in monocytes. H(1) receptor protein was undetectable in monocytes, whereas it was conspicuous in MDMs. Simultaneous analysis of H(2) and H(1) mRNA expression indicated that the H(2)/H(1) ratio decreased from 202.7 +/- 14.8 in monocytes to 2.2 +/- 0.4 in MDM and 39.5 +/- 5.0 in DCs. Incubation of monocytes with histamine neither affected intracellular Ca(2+) concentrations nor influenced IL-8 production. In contrast, histamine rapidly induced a Ca(2+) signal and stimulated IL-8 production in MDMs. Both effects were inhibited by H(1) blockade with levocetirizine, but not by H(2) blockade with ranitidine.


CONCLUSIONS
Differentiation of monocytes into macrophages or dendritic cells is associated with profound changes of histamine receptor expression. Upregulation of H(1) receptors confers on macrophages the capacity of being activated by histamine.


CONCLUSIONS
Regulation of H(1) and H(2) receptor expression in the monocyte/macrophage lineage can be relevant to the pathogenesis of allergic inflammation.
Triggiani
Massimo
M
Division of Clinical Immunology and Allergy, University of Naples Federico II, Naples, Italy. triggian@unina.it <triggian@unina.it>
Petraroli
Angelica
A
Loffredo
Stefania
S
Frattini
Annunziata
A
Granata
Francescopaolo
F
Morabito
Paolo
P
Staiano
Rosaria Ilaria
RI
Secondo
Agnese
A
Annunziato
Lucio
L
Marone
Gianni
G
D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011969:Receptors, Histamine H1 / Q000032:analysis / Q000235:genetics*; D011970:Receptors, Histamine H2 / Q000235:genetics; D015854:Up-Regulation
D015850:Interleukin-6; D012333:RNA, Messenger; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D006632:Histamine; D002118:Calcium