Cysteinyl Leukotrienes Mediate Histamine Hypersensitivity Ex Vivo by Increasing Histamine Receptor Numbers

Overview

Journal Mol Med

Publisher Biomed Central

Specialties General Medicine
Molecular Biology

Date 1999 Dec 22

PMID 10602777

Citations 6

Authors

G Pynaert

J Grooten

S J van Deventer

M P Peppelenbosch

Affiliations

Soon will be listed here.

Abstract

Background: Hyperresponsiveness to histamine is a key feature of a variety of pathological conditions, including bronchial asthma, food allergy, colitis ulcerosa, and topical allergic disorders. Cells isolated from hyperresponsive individuals do not display exaggerated histamine responses ex vivo and thus the molecular mechanisms underlying histamine responsiveness remain obscure. Importantly, several in vivo observations implicate cysteinyl leukotrienes as possible mediators of increased histamine responses. We decided to investigate whether cysteinyl leukotrienes enhance the cellular reaction to histamine in cell types involved in pathological and immunological histamine hyperresponsiveness, as this might provide an in vitro system for studying histamine responsiveness and could shed light on the underlying molecular mechanisms.

Materials And Methods: Histamine responsiveness was determined by measuring histamine-induced prostaglandin E(2) production. Scatchard analysis was performed to determine the number of histamine H(1) receptors. Mouse macrophages, primary isolated human peripheral blood monocytes, and human umbilical smooth muscle cells were investigated before and after cysteinyl leukotriene stimulation.

Results: In all three cell types tested, cysteinyl leukotrienes instantaneously enhanced histamine-induced prostaglandin E(2) production. This increase in prostaglandin E(2) production coincided with the immediate and transient appearance of additional H(1) receptors on the plasma membrane.

Conclusions: Cysteinyl leukotrienes prime histamine responses by recruiting additional histamine receptors in immunologically relevant cell types in vitro.

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References

KAHLSON G, ROSENGREN E . New approaches to the physiology of histamine. Physiol Rev. 1968; 48(1):155-96. DOI: 10.1152/physrev.1968.48.1.155. View

Busse . Leukotrienes and inflammation . Am J Respir Crit Care Med. 1998; 157(6 Pt 1):S210-3. View

Barnes P, Chung K, Page C . Inflammatory mediators of asthma: an update. Pharmacol Rev. 1998; 50(4):515-96. View

Griffin M, Weiss J, Leitch A, McFadden Jr E, Corey E, Austen K . Effects of leukotriene D on the airways in asthma. N Engl J Med. 1983; 308(8):436-9. DOI: 10.1056/NEJM198302243080807. View

Goldie R, Spina D, Henry P, Lulich K, Paterson J . In vitro responsiveness of human asthmatic bronchus to carbachol, histamine, beta-adrenoceptor agonists and theophylline. Br J Clin Pharmacol. 1986; 22(6):669-76. PMC: 1401203. DOI: 10.1111/j.1365-2125.1986.tb02956.x. View

Kurosawa M, Tsukagoshi H . Inhibitory effect of a thromboxane A2 synthetase inhibitor OKY-046 on bronchial hyperresponsiveness to histamine, but not on airway wall thickening, induced by intravenous administration of leukotriene C4 in guinea-pigs. Pulm Pharmacol. 1993; 6(4):247-53. DOI: 10.1006/pulp.1993.1033. View

Werle E, Lorenz W . [Histamine and histidine decarboxylases in the thyroid and the thymus]. Biochem Pharmacol. 1966; 15(8):1059-70. DOI: 10.1016/0006-2952(66)90271-1. View

Kern R, Smith L, Patterson R, Krell R, Bernstein P . Characterization of the airway response to inhaled leukotriene D4 in normal subjects. Am Rev Respir Dis. 1986; 133(6):1127-32. DOI: 10.1164/arrd.1986.133.6.1127. View

Barnes P . Biochemistry of asthma. Trends Biochem Sci. 1991; 16(10):365-9. DOI: 10.1016/0968-0004(91)90152-l. View

10.

Desmedt M, Rottiers P, Dooms H, Fiers W, Grooten J . Macrophages induce cellular immunity by activating Th1 cell responses and suppressing Th2 cell responses. J Immunol. 1998; 160(11):5300-8. View

11.

Fukushima C, Shimoda T, Matsuse H, Matsuo N, TAKAO A, Obase Y . In vitro responses to antigen stimulation: comparison between human lung parenchyma resected from asthmatic patients and non-asthmatic patients. Ann Allergy Asthma Immunol. 1999; 82(2):179-84. DOI: 10.1016/S1081-1206(10)62594-X. View

12.

Arm J, Spur B, Lee T . The effects of inhaled leukotriene E4 on the airway responsiveness to histamine in subjects with asthma and normal subjects. J Allergy Clin Immunol. 1988; 82(4):654-60. DOI: 10.1016/0091-6749(88)90979-7. View

13.

Kaye M, Smith L . Effects of inhaled leukotriene D4 and platelet-activating factor on airway reactivity in normal subjects. Am Rev Respir Dis. 1990; 141(4 Pt 1):993-7. DOI: 10.1164/ajrccm/141.4_Pt_1.993. View

14.

Thien F, Walters E . Eicosanoids and asthma: an update. Prostaglandins Leukot Essent Fatty Acids. 1995; 52(5):271-88. DOI: 10.1016/0952-3278(95)90027-6. View

15.

Meurs H, Koeter G, Kauffman H, Timmermans A, FOLKERS B, de Vries K . Reduced adenylate cyclase responsiveness to histamine in lymphocyte membranes of allergic asthmatic patients after allergen challenge. Int Arch Allergy Appl Immunol. 1985; 76(3):256-60. DOI: 10.1159/000233701. View

16.

Lee T, Austen K, Corey E, Drazen J . Leukotriene E4-induced airway hyperresponsiveness of guinea pig tracheal smooth muscle to histamine and evidence for three separate sulfidopeptide leukotriene receptors. Proc Natl Acad Sci U S A. 1984; 81(15):4922-5. PMC: 391604. DOI: 10.1073/pnas.81.15.4922. View

17.

Bloemers S, Verheule S, Peppelenbosch M, Smit M, Tertoolen L, de Laat S . Sensitization of the histamine H1 receptor by increased ligand affinity. J Biol Chem. 1998; 273(4):2249-55. DOI: 10.1074/jbc.273.4.2249. View

18.

OHickey S, Hawksworth R, Fong C, Arm J, Spur B, Lee T . Leukotrienes C4, D4, and E4 enhance histamine responsiveness in asthmatic airways. Am Rev Respir Dis. 1991; 144(5):1053-7. DOI: 10.1164/ajrccm/144.5.1053. View

19.

Bjorck T, Gustafsson L, Dahlen S . Isolated bronchi from asthmatics are hyperresponsive to adenosine, which apparently acts indirectly by liberation of leukotrienes and histamine. Am Rev Respir Dis. 1992; 145(5):1087-91. DOI: 10.1164/ajrccm/145.5.1087. View

20.

Hill S, Ganellin C, Timmerman H, Schwartz J, Shankley N, Young J . International Union of Pharmacology. XIII. Classification of histamine receptors. Pharmacol Rev. 1997; 49(3):253-78. View