Leukotriene B4-activated human endothelial cells promote transendothelial neutrophil migration

Nohgawa, Masaharu; Sasada, Masataka; Maeda, Akinori; Asagoe, Kohsuke; Harakawa, Nari; Takano, Kuniko; Yamamoto, Kokichi; Okuma, Minoru

doi:10.1002/jlb.62.2.203

Cited by 40 publications

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“…LTB 4 is a potent stimulus for PMNL adhesion to EC (5,40). At nanomolar concentrations, this lipid induces rolling PMNL to stick to postcapillary venules, thereby inducing prominent plasma leakage at these sites (41) and stimulates transendothelial migration in vitro (42). Similar observations of the biological activity of LTB 4 have been reported and reviewed (43), but all indicate that the production of LTB 4 by EC could be an important feed-forward signal during the development of inflammation by generating an intense local gradient of this chemotactic, PMNL-activating 32 P]ATP as described under "Experimental Procedures."…”

Section: Discussionmentioning

confidence: 99%

Regulation of Leukotriene A4 Hydrolase Activity in Endothelial Cells by Phosphorylation

Rybina

Liu

Gor

et al. 1997

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Regulation of Leukotriene A4 Hydrolase Activity in Endothelial Cells by Phosphorylation

Rybina

Liu

Gor

et al. 1997

Journal of Biological Chemistry

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“…However, the molecular mechanisms of LTB 4 -induced transendothelial migration of neutrophils is not fully understood, but seems to involve soluble factors as well as activation of both leukocyte and endothelial cell adhesion molecules (23). Direct effects of LTB 4 on endothelial cells have also been discussed, although these cells have appeared only weakly, if at all, reactive to this mediator (24,25). In this study, we sought to identify factors that might turn on BLT receptor expression and function in these cells.…”

Section: Effects Of Ltb4 On Nitrite Generation and Mcp-1 Release Frommentioning

confidence: 99%

Differential induction of BLT receptor expression on human endothelial cells by lipopolysacharide, cytokines, and leukotriene B₄

Qiu

Johansson

Sjöström

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Leukotriene (LT) B4 is a powerful chemotactic and immune modulating agent that signals via two receptors denoted BLT1 and BLT2.Here we report that BLT1 and BLT2 are expressed at low levels in an apparently silent state in human umbilical vein endothelial cells (HUVEC). However, treatment with LPS leads to a >10 fold increase in the levels of BLT1 mRNA without any significant effects on BLT2 mRNA. In parallel, LPS also increases the amounts of BLT1 protein.Tumor necrosis factor-␣ (TNF-␣) increases the expression of BLT2 mRNA Ϸ6 times above basal levels with only a modest increase in BLT1 mRNA. Interleukin-1␤ causes variable and parallel increases of both BLT1 and BLT2 mRNA. The natural ligand LTB4 also increases BLT1, but not BLT2, mRNA and protein expression. Along with the induction of BLT1 and͞or BLT2, HUVEC acquire the capacity to respond to LTB4 with increased levels of intracellular calcium and these signals can be blocked by isotype selective BLT antagonists, CP-105696 and LY-255283. In addition, treatment of HUVEC with LTB4 causes increased release of both nitrite, presumably reflecting nitric oxide (NO), and monocyte chemoattractant protein-1. Our data indicate that expression of functional BLT receptors may occur at the surface of endothelial cells in response to LPS, cytokines, and ligand, which in turn may have functional consequences during the early vascular responses to inflammation. Moreover, the results point to BLT receptors as potential targets for pharmacological intervention in LT-dependent inflammatory diseases such as asthma, rheumatoid arthritis, and arteriosclerosis.inflammation ͉ arteriosclerosis ͉ rheumatoid arthritis ͉ asthma ͉ nitric oxide T he leukotrienes (LTs) are a family of lipid mediators that play important roles in a variety of allergic and inflammatory reactions (1, 2). These molecules are divided into two classes, the spasmogenic cysteinyl-LTs (cys-LT) and LTB 4 , which is a classical nM chemotactic agent produced by neutrophils, macrophages, and mast cells. Thus, LTB 4 is a potent chemoattractant for polymorphonuclear leukocytes, comparable to complement peptide C5a and fMet-Leu-Phe (3, 4). Recent data also indicate that LTB 4 is a strong chemoattractant for T cells, creating a functional link between early innate and late adaptive immune responses (5-7). Because of these biological effects, LTB 4 is regarded as an important chemical mediator in a variety of acute and chronic inflammatory diseases and only recently, genetic and biochemical evidence strongly implicate LTB 4 as a mediator of vascular inflammation and arteriosclerosis (8-10). LTB 4 , is synthesized from arachidonic acid via the concerted action of 5-lipoxygenase, assisted by 5-lipoxygenase-activating protein and the terminal LTA 4 hydrolase (11), usually in a single cell or via transcellular routes; this mechanism has been shown to occur in vivo (12,13). LTB 4 signals primarily via a specific, high-affinity, G proteincoupled seven-transmembrane receptor, termed BLT 1 (14). The BLT 1 gene is located on the huma...

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“…15 Cysteinyl leucotrienes are major mediators of inflammation, potent neutrophil chemoattractants and activators. 17 Up regulation of cysteinyl leucotriene receptor has been found in the tonsils of children undergoing tonsillectomy for OSA. 18 Montelukast, a cysteinyl leckotriene receptor antagonist, induced reductions in adenoidal size and respiratory-related sleep disturbances.…”

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Induced sputum inflammatory measures correlate with disease severity in children with obstructive sleep apnoea

Hung

Tsang

et al. 2007

Thorax

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Objective: To establish the association between airway inflammation and severity of obstructive sleep apnoea (OSA) in children. Methods: Consecutive children presenting with symptoms suggestive of OSA were recruited. They completed a sleep apnoea symptom questionnaire, underwent physical examination, spirometry, sputum induction and an overnight polysomnography. Adequate sputum contained ,50% squamous epithelial cells, and OSA was diagnosed if the obstructive apnoea index was .1. Results: 73 children with a median (interquartile range (IQR)) age of 11.3 (10.0-13.2) years were recruited. There were 21 girls and the median body mass index of the group was 24.0 (18.0-27.0) kg/m 2 . The most common presenting symptoms were habitual snoring, mouth breathing and prone sleeping position. Sputum induction was successful in 43 (59%) children, of whom 14 were found to have OSA. Children with OSA had significantly greater percentage sputum neutrophil than those without OSA (18.5 (IQR 8.0-42.0) v 4 (IQR 3.0-11.3), p = 0.006). On multiple regression analysis, percentage sputum neutrophil was significantly associated with OSA (odds ratio = 1.1, p = 0.013). Conclusion: Children with OSA had airway inflammation characterised by a marked increase in neutrophils. Further studies are needed to confirm these findings and to better define the downstream cellular interactions and molecular pathogenesis in childhood OSA.

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Leukotriene B4-activated human endothelial cells promote transendothelial neutrophil migration

Abstract: Abstract:We explored the effect of leukotriene B4

Cited by 40 publications

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Regulation of Leukotriene A4 Hydrolase Activity in Endothelial Cells by Phosphorylation

Regulation of Leukotriene A4 Hydrolase Activity in Endothelial Cells by Phosphorylation

Differential induction of BLT receptor expression on human endothelial cells by lipopolysacharide, cytokines, and leukotriene B₄

Induced sputum inflammatory measures correlate with disease severity in children with obstructive sleep apnoea

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Leukotriene B4-activated human endothelial cells promote transendothelial neutrophil migration

Abstract: Abstract:We explored the effect of leukotriene B4

Cited by 40 publications

References 0 publications

Regulation of Leukotriene A4 Hydrolase Activity in Endothelial Cells by Phosphorylation

Regulation of Leukotriene A4 Hydrolase Activity in Endothelial Cells by Phosphorylation

Differential induction of BLT receptor expression on human endothelial cells by lipopolysacharide, cytokines, and leukotriene B4

Induced sputum inflammatory measures correlate with disease severity in children with obstructive sleep apnoea

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Differential induction of BLT receptor expression on human endothelial cells by lipopolysacharide, cytokines, and leukotriene B₄