5-Lipoxygenase products regulate basophil functions: 5-Oxo-ETE elicits migration, and leukotriene B4 induces degranulation

Iikura, Motoyasu; Suzukawa, Maho; Yamaguchi, Masao; Sekiya, Takashi; Komiya, Akiko; Yoshimura-Uchiyama, Chitose; Nagase, Hiroyuki; Matsushima, Kouji; Yamamoto, Kazuhiko; Hirai, Koichi

doi:10.1016/j.jaci.2005.04.029

Cited by 37 publications

(93 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…T he arachidonic acid metabolite leukotriene B 4 (LTB 4 ) is predominantly produced by neutrophils and, to a lesser extent, by monocytes/macrophages, dendritic cells, and mast cells (1). LTB 4 exerts a diverse range of effects on the function of these latter immune cells (2) and also the activity of eosinophils, basophils, and lymphocytes (3)(4)(5)(6)(7)(8).…”

mentioning

confidence: 99%

“…LTB 4 exerts a diverse range of effects on the function of these latter immune cells (2) and also the activity of eosinophils, basophils, and lymphocytes (3)(4)(5)(6)(7)(8). Most, if not all, of these immune functions are associated with the BLT1 receptor, with BLT2 generally more associated with cancer progression (9).…”

mentioning

confidence: 99%

“…LTB 4 in turn is a potent inducer of a variety of leukocyte signaling events, including Ca 2+ mobilization, activation of PI3K/protein kinase B signaling pathways, adhesion of granulocytes to endothelial cells, and neutrophil chemotaxis, degranulation, and reactive oxygen species production (2). These cell functions are essential immune responses; however, increased release of LTB 4 by inflammatory cells at the site of inflammation can influence the extent of the local inflammatory response (14), driving goblet cell hyperplasia, mucus hypersecretion, and airway hyperresponsiveness (10)(11)(12)(13).…”

mentioning

confidence: 99%

“…Overproduction of LTB 4 is associated with a number of airway diseases, including bronchial asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF), and other inflammatory disorders, including psoriasis and rheumatoid arthritis (RA) (15)(16)(17)(18)(19). High levels of LTB 4 in synovial tissues have been reported in RA, with BLT1 expression on infiltrating neutrophils a necessity for arthritis development (10,19).…”

mentioning

confidence: 99%

“…High levels of LTB 4 in synovial tissues have been reported in RA, with BLT1 expression on infiltrating neutrophils a necessity for arthritis development (10,19). Moreover, levels of LTB 4 correlate with severity of airways disease in individuals with CF (20) and asthma (21), and they are found associated with development of Th2 cytokine mediated airway hyperresponsiveness (22). Of major importance, LTB 4 levels in COPD or asthmatic individuals are unaffected by corticosteroid treatment (23), emphasizing the need for therapeutic intervention to alleviate LTB 4 -induced inflammation.…”

mentioning

confidence: 99%

See 4 more Smart Citations

The BLT1 Inhibitory Function of α-1 Antitrypsin Augmentation Therapy Disrupts Leukotriene B4 Neutrophil Signaling

O’Dwyer

O’Brien

Wormald

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

Leukotriene B4 (LTB4) contributes to many inflammatory diseases, including genetic and nongenetic forms of chronic obstructive pulmonary disease. α-1 Antitrypsin (AAT) deficiency (AATD) is characterized by destruction of lung parenchyma and development of emphysema, caused by low AAT levels and a high neutrophil burden in the airways of affected individuals. In this study we assessed whether AATD is an LTB4-related disease and investigated the ability of serum AAT to control LTB4 signaling in neutrophils. In vitro studies demonstrate that neutrophil elastase is a key player in the LTB4 inflammatory cycle in AATD, causing increased LTB4 production, and associated BLT1 membrane receptor expression. AATD patients homozygous for the Z allele were characterized by increased neutrophil adhesion and degranulation responses to LTB4. We demonstrate that AAT can bind LTB4 and that AAT/LTB4 complex formation modulates BLT1 engagement and downstream signaling events, including 1,4,5-triphosphate production and Ca2+ flux. Additionally, treatment of ZZ-AATD individuals with AAT augmentation therapy decreased plasma LTB4 concentrations and reduced levels of membrane-bound neutrophil elastase. Collectively, these results provide a mechanism by which AAT augmentation therapy impacts on LTB4 signaling in vivo, and not only reinforces the utility of this therapy for resolving inflammation in AATD, but supports useful future clinical applications in treatment of other LTB4-related diseases.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

The BLT1 Inhibitory Function of α-1 Antitrypsin Augmentation Therapy Disrupts Leukotriene B4 Neutrophil Signaling

O’Dwyer

O’Brien

Wormald

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

5-Oxo-ETE and Inflammation

Powell

Rokach

2016

Lipoxygenases in Inflammation

View full text Add to dashboard Cite

Expanding roles for leukotrienes in airway inflammation

Peters‐Golden

2008

Curr Allergy Asthma Rep

View full text Add to dashboard Cite

Leukotrienes (LTs) are lipid mediators derived from the 5-lipoxygenase pathway of arachidonic acid metabolism. Cysteinyl (cys) LTs C(4), D(4), and E(4) are long known to contribute to airway contractile responses via ligation of the cysLT1 receptor, and cysLT1 antagonists are beneficial in some patients with asthma. Research advances over the past several years suggest that cysLT1 also mediates the ability of cysLTs to modulate inflammation, immune responses, and airway remodeling. Although less is known about an additional receptor, cysLT2, emerging evidence indicates that it likely also contributes to cysLT actions promoting inflammation, vascular permeability, and perhaps fibrosis. LTB(4), best known as a neutrophil chemoattractant, is now recognized to exert other important effects contributing to inflammatory and immune responses. These recent data highlight a growing appreciation for LTs as pleiotropic effectors, which are integral components in the network of molecules that mediate the expression of asthma.

show abstract

5-Lipoxygenase products regulate basophil functions: 5-Oxo-ETE elicits migration, and leukotriene B4 induces degranulation

Cited by 37 publications

References 40 publications

The BLT1 Inhibitory Function of α-1 Antitrypsin Augmentation Therapy Disrupts Leukotriene B4 Neutrophil Signaling

The BLT1 Inhibitory Function of α-1 Antitrypsin Augmentation Therapy Disrupts Leukotriene B4 Neutrophil Signaling

5-Oxo-ETE and Inflammation

Expanding roles for leukotrienes in airway inflammation

Contact Info

Product

Resources

About