Histamine‐induced inhibition of leukotriene biosynthesis in human neutrophils: involvement of the H2 receptor and cAMP
Open Access
- 1 February 2004
- journal article
- Published by Wiley in British Journal of Pharmacology
- Vol. 141 (4), 552-561
- https://doi.org/10.1038/sj.bjp.0705654
Abstract
1. Histamine is generally regarded as a pro-inflammatory mediator in diseases such as allergy and asthma. A growing number of studies, however, suggest that this autacoid is also involved in the downregulation of human polymorphonuclear leukocyte (PMN) functions and inflammatory responses through activation of the Gs-coupled histamine H(2) receptor. 2. We report here that histamine inhibits thapsigargin- and ligand (PAF and fMLP)-induced leukotriene (LT) biosynthesis in human PMN in a dose-dependent manner. 3. The suppressive effect of histamine on LT biosynthesis was abrogated by the histamine H(2) receptor antagonists cimetidine, ranitidine, and tiotidine. In contrast, the histamine H(1), H(3), and H(4) receptor antagonists used in this study were ineffective in counteracting the inhibitory effect of histamine on the biosynthesis of LT in activated human PMN. 4. The inhibition of LT biosynthesis by histamine was characterized by decreased arachidonic acid release and 5-lipoxygenase translocation to the nuclear membrane. 5. Incubation of PMN with the cAMP-dependent protein kinase (PKA) inhibitor N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide prevented the inhibitory effect of histamine on LT biosynthesis, suggesting an important role for PKA in this effect of histamine on LT biosynthesis in PMN. 6. These data provide the first evidences that, similarly to adenosine and prostaglandin E(2), histamine is a potent suppressor of LT biosynthesis, and support the concept that histamine may play a dual role in the regulation of inflammation.Keywords
This publication has 66 references indexed in Scilit:
- Colocalization of Cytosolic Phospholipase A2, 5‐Lipoxygenase, and 5‐Lipoxygenase‐Activating Protein at the Nuclear Membrane of A23187‐Stimulated Human NeutrophilsJBIC Journal of Biological Inorganic Chemistry, 1996
- Histamine Augments VCAM-1 Expression on IL-4- and TNF-α-Stimulated Human Umbilical Vein Endothelial CellsInternational Archives of Allergy and Immunology, 1996
- Involvement of cyclic AMP in the effects of phosphodiesterase IV inhibitors on arachidonate release from mononuclear cellsEuropean Journal of Pharmacology: Molecular Pharmacology, 1995
- Leukotriene B4 production by blood neutrophils in allergic rhinitis—effects of cetirizineClinical and Experimental Allergy, 1995
- Downward regulation of neutrophil infiltration by endogenous histamine without affecting vascular permeability responses in air-pouch-type carrageenin inflammation in ratsInflammation, 1991
- Inhibitory effects of histamine H1 receptor blocking drugs on metabolic activations of neutrophils.Journal of Pharmacobio-Dynamics, 1991
- Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules: in vivo effects with relevance to the acute inflammatory response.Proceedings of the National Academy of Sciences of the United States of America, 1981
- Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytesNature, 1980
- Dimaprit inhibition of zymosan-stimulated beta-glucuronidase release from human granulocytesInflammation Research, 1980
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970