+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Roles of 5-lipoxygenase and cysteinyl-leukotriene type 1 receptors in the hematological response to allergen challenge and its prevention by diethylcarbamazine in a murine model of asthma

Roles of 5-lipoxygenase and cysteinyl-leukotriene type 1 receptors in the hematological response to allergen challenge and its prevention by diethylcarbamazine in a murine model of asthma

Mediators of Inflammation 2014: 403970

Diethylcarbamazine (DEC), which blocks leukotriene production, abolishes the challenge-induced increase in eosinopoiesis in bone-marrow from ovalbumin- (OVA-) sensitized mice, suggesting that 5-lipoxygenase (5-LO) products contribute to the hematological responses in experimental asthma models. We explored the relationship between 5-LO, central and peripheral eosinophilia, and effectiveness of DEC, using PAS or BALB/c mice and 5-LO-deficient mutants. We quantified eosinophil numbers in freshly harvested or cultured bone-marrow, peritoneal lavage fluid, and spleen, with or without administration of leukotriene generation inhibitors (DEC and MK886) and cisteinyl-leukotriene type I receptor antagonist (montelukast). The increase in eosinophil numbers in bone-marrow, observed in sensitized/challenged wild-type mice, was abolished by MK886 and DEC pretreatment. In ALOX mutants, by contrast, there was no increase in bone-marrow eosinophil counts, nor in eosinophil production in culture, in response to sensitization/challenge. In sensitized/challenged ALOX mice, challenge-induced migration of eosinophils to the peritoneal cavity was significantly reduced relative to the wild-type PAS controls. DEC was ineffective in ALOX mice, as expected from a mechanism of action dependent on 5-LO. In BALB/c mice, challenge significantly increased spleen eosinophil numbers and DEC treatment prevented this increase. Overall, 5-LO appears as indispensable to the systemic hematological response to allergen challenge, as well as to the effectiveness of DEC.

(PDF emailed within 0-6 h: $19.90)

Accession: 058791992

Download citation: RISBibTeXText

PMID: 25477712

DOI: 10.1155/2014/403970

Related references

Leukotriene C4 synthase genetic polymorphism directs urinary cysteinyl-leukotriene response to aspirin challenge in asthma. European Journal of Clinical Investigation 28(SUPPL 1): A52, 1998

Contrasting effects of allergen challenge on airway responsiveness to cysteinyl leukotriene D(4) and methacholine in mild asthma. Thorax 57(7): 575-580, 2002

Angiogenesis in response to allergen challenge in a murine model of asthma. Journal of Allergy & Clinical Immunology 113(2 Supplement): S190, February, 2004

Characterization of cysteinyl leukotriene-related receptors and their interactions in a mouse model of asthma. Prostaglandins, Leukotrienes, and Essential Fatty Acids 141: 17-23, 2019

Effects of ONO-6950, a novel dual cysteinyl leukotriene 1 and 2 receptors antagonist, in a guinea pig model of asthma. European Journal of Pharmacology 765: 242-248, 2016

Allergen challenge induces Ifng dependent GTPases in the lungs as part of a Th1 transcriptome response in a murine model of allergic asthma. Plos One 4(12): E8172, 2010

Effects of JNJ-40929837, a leukotriene A4 hydrolase inhibitor, in a bronchial allergen challenge model of asthma. Pulmonary Pharmacology and Therapeutics 29(1): 15-23, 2016

Cysteinyl-leukotriene type 1 receptors transduce a critical signal for the up-regulation of eosinophilopoiesis by interleukin-13 and eotaxin in murine bone marrow. Journal of Leukocyte Biology 87(5): 885-893, 2010

Defining the genomic response to allergen challenge in murine asthma. Journal of Allergy & Clinical Immunology 111(2 Abstract Supplement): S270, February, 2003

P2Y1 and cysteinyl leukotriene receptors mediate purine and cysteinyl leukotriene co-release in primary cultures of rat microglia. International Journal of Immunopathology and Pharmacology 18(2): 255-268, 2005

Inhibition of the leukotriene synthetase of rat basophil leukemia cells by diethylcarbamazine, and synergism between diethylcarbamazine and piriprost, a 5-lipoxygenase inhibitor. Biochemical Pharmacology 35(3): 425-433, 1986

The effects of low dose leukotriene receptor antagonist therapy on airway remodeling and cysteinyl leukotriene expression in a mouse asthma model. Experimental & Molecular Medicine 38(2): 109-118, 2006

Cysteinyl leukotriene receptors, old and new; implications for asthma. Clinical and Experimental Allergy 42(9): 1313-1320, 2013

Implication of 5-lipoxygenase/cysteinyl leukotriene receptors and histamine/histamine receptors in brain disease. Zhejiang Da Xue Xue Bao. Yi Xue Ban 36(2): 105-110, 2007

Effect of a 5-lipoxygenase inhibitor on leukotriene generation and airway responses after allergen challenge in asthmatic patients. Thorax 46(3): 184-189, 1991