Early suppression of basophil activation during allergen-specific immunotherapy by histamine receptor 2.
BACKGROUND
Early desensitization of FcεRI-bearing mast cells and basophils has been demonstrated in allergen-specific immunotherapy and drug desensitization. However, its mechanisms have not been elucidated in detail. Histamine is one of the main mediators released on FcεRI triggering of basophils and mast cells, and it exerts its functions through histamine receptors (HRs).


OBJECTIVE
We sought to investigate HR expression on basophils of patients undergoing venom immunotherapy (VIT) and its effect on allergen, IgE, and FcεRI cross-linking-mediated basophil function and mediator release.


METHODS
Basophils were purified from the peripheral blood of patients undergoing VIT and control subjects and were studied functionally by using real-time PCR, flow cytometry and ELISA assays.


RESULTS
Rapid upregulation of H2R within the first 6 hours of the build-up phase of VIT was observed. H2R strongly suppressed FcεRI-induced activation and mediator release of basophils, including histamine and sulfidoleukotrienes, as well as cytokine production in vitro.


CONCLUSIONS
Immunosilencing of FcεRI-activated basophils by means of selective suppression mediated by H2R might be highly relevant for the very early induction of allergen tolerance and the so-called desensitization effect of VIT.
Department of Dermatology and Allergy, University of Bonn, Bonn, Germany. Natalija.Novak@ukb.uni-bonn.de
Natalija
N
Novak
Nihal
N
Mete
Caroline
C
Bussmann
Laura
L
Maintz
Thomas
T
Bieber
Mübeccel
M
Akdis
Judith
J
Zumkehr
Marek
M
Jutel
Cezmi
C
Akdis
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001491:Basophils / Q000187:drug effects* / Q000276:immunology; D001514:Bee Venoms / Q000627:therapeutic use; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy*; D007165:Immunosuppression Therapy; D007299:Insect Bites and Stings / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011970:Receptors, Histamine H2 / Q000378:metabolism*; D017455:Receptors, IgE / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014688:Venoms / Q000627:therapeutic use*; D014862:Wasp Venoms / Q000652:urine; D055815:Young Adult
D001514:Bee Venoms; C543355:FcepsilonRI alpha-chain, human; D011970:Receptors, Histamine H2; D017455:Receptors, IgE; D014688:Venoms; D014862:Wasp Venoms