Leukotriene B4 costimulates 5-lipoxygenase activity in neutrophils via increased 5-lipoxygenase translocation

Serio, Kenneth J.; Baker, Joseph; Ring, William L.; Riddick, Carl A.; Bigby, Timothy D.

doi:10.1152/ajpcell.1997.272.4.c1329

Cited by 9 publications

(6 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cells were harvested and stimulated with the calcium ionophore, A23187 (at 1 M), with LTC 4 release quantitated by ELISA. Calcium ionophore stimulation has been shown to elicit LT release in previous studies (38,39). LPS conditioning for 7 days significantly decreased ionophore-stimulated LTC 4 release from THP-1 cells, as compared with control (0.33 ϩ 0.03 vs 1.13 ϩ 0.03 ng LTC 4 released per million cells; mean ϩ SEM; n ϭ 4, p Ͻ 0.0001, respectively) ( Fig.…”

Section: Lps Conditioning Decreases Calcium Ionophore-stimulated Ltc mentioning

confidence: 59%

Lipopolysaccharide Down-Regulates the Leukotriene C4 Synthase Gene in the Monocyte-Like Cell Line, THP-1

Serio

Johns

Luo

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

We studied the effects of LPS on cysteinyl leukotriene (LT) synthesis and LTC4 synthase expression in mononuclear phagocytes. Conditioning of the monocyte-like cell line, THP-1, with LPS for 7 days resulted in significantly decreased ionophore-stimulated LTC4 release. The putative LPS receptor, Toll-like receptor 4, was expressed in THP-1 cells. LPS down-regulated LTC4 synthase mRNA in THP-1 cells in a dose- and time-dependent manner, with down-regulation observed as early as 4 h. Conditioning of actinomycin D-treated cells with LPS resulted in no change in the rate of LTC4 synthase mRNA decay. LPS treatment of THP-1 cells, transiently transfected with a LTC4 synthase promoter (1.35 kb)-reporter construct, decreased promoter activity. Neutralization of TNF-α and inhibition of mitogen-activated protein kinase kinase/extracellular signal-regulated kinase did not inhibit the effect of LPS. Treatment of cells with a Toll-like receptor 4-blocking Ab and an inhibitor of NF-κB activation resulted in inhibition of the LPS effect, while activation of NF-κB and p50/p65 overexpression down-regulated the LTC4 synthase gene. LPS down-regulates cysteinyl LT release and LTC4 synthase gene expression in mononuclear phagocytes by an NF-κB-mediated mechanism.

show abstract

Section: Lps Conditioning Decreases Calcium Ionophore-stimulated Ltc mentioning

confidence: 59%

Lipopolysaccharide Down-Regulates the Leukotriene C4 Synthase Gene in the Monocyte-Like Cell Line, THP-1

Serio

Johns

Luo

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Previous studies have also suggested that LTB 4 secretion could act as a paracrine effector for efficient neutrophil activation and degranulation in response to LTB 4 or ATP, respectively (Kannan, 2002; Serio et al, 1997). We predict that both in vivo and in vitro , the secondary gradient generated by the secretion of LTB 4 can efficiently recruit a population of neutrophils that may not normally be recruited to sites of inflammation.…”

Section: Discussionmentioning

confidence: 99%

LTB4 Is a Signal-Relay Molecule during Neutrophil Chemotaxis

et al. 2012

View full text Add to dashboard Cite

SUMMARY Neutrophil recruitment to inflammation sites purportedly depends on sequential waves of chemoattractants. Current models propose that leukotriene B4 (LTB4), a secondary chemoattractant secreted by neutrophils in response to primary chemoattractants such as formyl-peptides, is important in initiating the inflammation process. In this study, we demonstrate that LTB4 plays a central role in neutrophil activation and migration to formyl-peptides. We show that LTB4 production dramatically amplifies formyl-peptide-mediated neutrophil polarization and chemotaxis by regulating specific signaling pathways acting upstream of actin polymerization and MyoII phosphorylation. Importantly, by analyzing the migration of neutrophils isolated from wild-type mice and mice lacking the formyl peptide receptor 1, we demonstrate that LTB4 acts as a signal to relay information from cell-to-cell over long distances. Together, our findings imply that LTB4 is a signal relay molecule that exquisitely regulates neutrophils chemotaxis to formyl peptides, which are produced at the core of inflammation sites.

show abstract

“…However, in mast cell-independent models and in models of established disease, the source of LTB4 is not established. Because granulocytes are a major source of LTB4 (47) and LTB4 may further stimulate 5-lipoxygenase activity in these cells (48), it thus is possible that increased neutrophil recruitment into the airways amplifies LTB4 production and cellular activation. Definition of abbreviations: mU/ml 5 ELISA mUnits/ml; OVA/OVA/BLT1i 5 sensitized and challenged mice followed by treatment with BLT1 antagonist; OVA/OVA/ vehicle 5 sensitized and challenged mice followed by vehicle treatment; PBS/OVA/BLT1i 5 nonsensitized but challenged mice followed by treatment with BLT1 antagonist; PBS/OVA/vehicle 5 nonsensitized but challenged mice followed by treatment with vehicle.…”

Section: Discussionmentioning

confidence: 99%

Blocking the Leukotriene B4 Receptor 1 Inhibits Late-Phase Airway Responses in Established Disease

Waseda

Miyahara

Kanehiro

et al. 2011

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Most of the studies investigating the effectiveness of blocking the leukotriene B4 (LTB4) receptor 1 (BLT1) have been performed in models of primary or acute allergen challenge. The role of the LTB4-BLT1 pathway in secondary challenge models, where airway hyperresponsiveness (AHR) and airway inflammation have been established, has not been defined. We investigated the effects of blocking BLT1 on early-and late-phase development of AHR and airway inflammation in previously sensitized and challenged mice. Female BALB/c mice were sensitized (Days 1 and 14) and challenged (primary, Days 28-30) with ovalbumin. On Day 72, mice were challenged (secondary) with a single OVA aerosol, and the early and late phases of AHR and inflammation were determined. Specific blockade of BLT1 was attained by oral administration of a BLT1 antagonist on Days 70 through 72. Administration of the antagonist inhibited the secondary ovalbumin challenge-induced alterations in airway responses during the late phase but not during the early phase, as demonstrated by decreases in AHR and in bronchoalveolar lavage neutrophilia and eosinophilia 6 and 48 hours after secondary challenge. The latter was associated with decreased levels of KC protein, macrophage inflammatory protein 2, and IL-17 in the airways. These data identify the importance of the LTB4-BLT1 pathway in the development of late-phase, allergen-induced airway responsiveness after secondary airway challenge in mice with established airway disease.

show abstract

Leukotriene B4 costimulates 5-lipoxygenase activity in neutrophils via increased 5-lipoxygenase translocation

Cited by 9 publications

References 10 publications

Lipopolysaccharide Down-Regulates the Leukotriene C4 Synthase Gene in the Monocyte-Like Cell Line, THP-1

Lipopolysaccharide Down-Regulates the Leukotriene C4 Synthase Gene in the Monocyte-Like Cell Line, THP-1

LTB4 Is a Signal-Relay Molecule during Neutrophil Chemotaxis

Blocking the Leukotriene B4 Receptor 1 Inhibits Late-Phase Airway Responses in Established Disease

Contact Info

Product

Resources

About