help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bissonnette, E. Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bissonnette, E. Y.

Am. J. Respir. Cell Mol. Biol., Vol 14, No. 6, 06 1996, 620-626.

Histamine inhibits tumor necrosis factor alpha release by mast cells through H2 and H3 receptors

EY Bissonnette
Department of Medicine, University of Alberta, Edmonton, Canada.

Histamine was one of the first inflammatory mediators thought to be important in the pathophysiology of asthma, but it is not now thought to be a mediator with primary importance in airway constriction. However, histamine has several effects that may be relevant. One of these effects, its immunoregulatory role, has been largely ignored in asthma. Thus, because mast cells (MC) are an important source of histamine and cytokines, the modulation by histamine of the release of one cytokine, tumor necrosis factor alpha (TNF alpha), was investigated. Rat peritoneal MC (PMC) were pretreated with different concentrations of histamine (10(-14) to 10(-4) M) for 2 h before being tested for their TNF alpha-dependent cytotoxicity. A concentration- dependent inhibition of cytotoxicity was observed from 21% at 10(-12) M to 38% at 10(-4) M, reaching a plateau at 10(-8) M. At least 1 h pretreatment with histamine or its presence throughout the cytotoxic assay was required for the inhibitory effect of histamine. This inhibition was abrogated by indomethacin or anti-PGE2, suggesting that PGE2 may be an important mediator in the inhibition of TNF alpha by histamine. To investigate the type of histamine receptor implicated in this effect, PMC were treated for 20 min with H1 (clemastine and diphenhydramine), H2 (ranitidine and cimetidine), or H3 (thioperamide) receptor antagonists before the addition of histamine. H2 or H3 antagonists abrogated the inhibitory effect of histamine on PMC TNF alpha-dependent cytotoxicity. Furthermore, blockage of H2 receptors with ranitidine increased the release of TNF alpha from PMC stimulated with antigen, suggesting that histamine released by MC within 10 min of antigen stimulation downregulates the subsequent release of TNF alpha from the same MC population. These results suggest that histamine may act as an autocrine regulator of cytokine release by MC and thus modulate inflammatory responses in allergic asthma.


This article has been cited by other articles:


Home page
 J. Exp. Med.Home page
W. Beghdadi, A. Porcherie, B. S. Schneider, D. Dubayle, R. Peronet, M. Huerre, T. Watanabe, H. Ohtsu, J. Louis, and S. Mecheri
Inhibition of histamine-mediated signaling confers significant protection against severe malaria in mouse models of disease
J. Exp. Med., February 18, 2008; 205(2): 395 - 408.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
C. L. Hofstra, P. J. Desai, R. L. Thurmond, and W.-P. Fung-Leung
Histamine H4 Receptor Mediates Chemotaxis and Calcium Mobilization of Mast Cells
J. Pharmacol. Exp. Ther., June 1, 2003; 305(3): 1212 - 1221.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
A. Koarai, M. Ichinose, S. Ishigaki-Suzuki, S. Yamagata, H. Sugiura, E. Sakurai, Y. Makabe-Kobayashi, A. Kuramasu, T. Watanabe, K. Shirato, et al.
Disruption of L-Histidine Decarboxylase Reduces Airway Eosinophilia but not Hyperresponsiveness
Am. J. Respir. Crit. Care Med., March 1, 2003; 167(5): 758 - 763.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
C. Liu, X.-J. Ma, X. Jiang, S. J. Wilson, C. L. Hofstra, J. Blevitt, J. Pyati, X. Li, W. Chai, N. Carruthers, et al.
Cloning and Pharmacological Characterization of a Fourth Histamine Receptor (H4) Expressed in Bone Marrow
Mol. Pharmacol., March 1, 2001; 59(3): 420 - 426.
[Abstract] [Full Text]

Home page
 J. Immunol.Home page
J. Sirois, G. Menard, A. S. Moses, and E. Y. Bissonnette
Importance of Histamine in the Cytokine Network in the Lung Through H2 and H3 Receptors: Stimulation of IL-10 Production
J. Immunol., March 15, 2000; 164(6): 2964 - 2970.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
J. J. Rozniecki, R. Letourneau, M. Sugiultzoglu, C. Spanos, J. Gorbach, and T. C. Theoharides
Differential Effect of Histamine 3 Receptor-Active Agents on Brain, but not Peritoneal, Mast Cell Activation
J. Pharmacol. Exp. Ther., September 1, 1999; 290(3): 1427 - 1435.
[Abstract] [Full Text]

Home page
 Pharmacol. Rev.Home page
P. J. Barnes, K. F. Chung, and C. P. Page
Inflammatory Mediators of Asthma: An Update
Pharmacol. Rev., December 1, 1998; 50(4): 515 - 596.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
I. J. Elenkov, E. Webster, D. A. Papanicolaou, T. A. Fleisher, G. P. Chrousos, and R. L. Wilder
Histamine Potently Suppresses Human IL-12 and Stimulates IL-10 Production via H2 Receptors
J. Immunol., September 1, 1998; 161(5): 2586 - 2593.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 1996 American Thoracic Society.