Leukotriene B<sub>4</sub>: A highly potent and stereospecific factor stimulating migration of polymorphonuclear leukocytes

Malmsten, Curt; Palmblad, Jan; Udén, Ann-Mari; Rådmark, Olof; Engstedt, L.; Samuelsson, Bengt

doi:10.1111/j.1748-1716.1980.tb06696.x

Cited by 137 publications

(43 citation statements)

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“…67,68 They trigger immune response by recruitment and activation of leukocytes and play an essential role as mediators in pulmonary inflammation. 31,32 Several studies have shown that leukotriene B 4 (LTB 4 ) is involved in PAH pathogenesis. [69][70][71] Rodent models of PH, including MCT-and SU5416 (a VEGFR2 [vascular endothelial growth factor receptor 2] inhibitor)-treated rat models, have shown elevated levels of LTB 4 .…”

Section: Role Of Other Metabolites Of Aa In Pahmentioning

confidence: 99%

Role of Oxidized Lipids in Pulmonary Arterial Hypertension

et al. 2016

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Pulmonary arterial hypertension (PAH) is a multifactorial disease characterized by interplay of many cellular, molecular, and genetic events that lead to excessive proliferation of pulmonary cells, including smooth muscle and endothelial cells; inflammation; and extracellular matrix remodeling. Abnormal vascular changes and structural remodeling associated with PAH culminate in vasoconstriction and obstruction of pulmonary arteries, contributing to increased pulmonary vascular resistance, pulmonary hypertension, and right ventricular failure. The complex molecular mechanisms involved in the pathobiology of PAH are the limiting factors in the development of potential therapeutic interventions for PAH. Over the years, our group and others have demonstrated the critical implication of lipids in the pathogenesis of PAH. This review specifically focuses on the current understanding of the role of oxidized lipids, lipid metabolism, peroxidation, and oxidative stress in the progression of PAH. This review also discusses the relevance of apolipoprotein A-I mimetic peptides and microRNA-193, which are known to regulate the levels of oxidized lipids, as potential therapeutics in PAH.

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Section: Role Of Other Metabolites Of Aa In Pahmentioning

confidence: 99%

Role of Oxidized Lipids in Pulmonary Arterial Hypertension

et al. 2016

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“…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 human chromosome 14q11.2-q12 and SP1 binding to CpG regions appears to be important for basal transcription (15).…”

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“…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)(9)(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).…”

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confidence: 99%

“…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)(6)(7).…”

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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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Die Leukotriene, superaktive, an Allergie und Entzündung beteiligte Wirkstoffe

Samuelsson¹

2006

Angewandte Chemie

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Die Arachidonsaure, eine vierfach ungeslttigte C2,,-Fettslure, hat in den letzten 15 Jahren weit iiber den Kreis der Ernlhrungsforscher hinaus Interesse erheischt. Sie bildet einen Acylbestandteil der Phospholipide aller tierischen Zellen. Die schon lange bekannte Tatsache, daD bestimmte ungesiittigte Fettsguren in der Nahrung enthalten sein miissen, damit eine normale Funktion des Organismus gewlhrleistet ist, hat mit der Entdeckung einer weit aufgefacherten Palette von biologisch hochwirksamen Oxidationsprodukten der Arachidonsaure, einer Kaskade, wie sie oft genannt werden, eine Erklarung erfahren.

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Leukotriene B₄: A highly potent and stereospecific factor stimulating migration of polymorphonuclear leukocytes

Cited by 137 publications

References 10 publications

Role of Oxidized Lipids in Pulmonary Arterial Hypertension

Role of Oxidized Lipids in Pulmonary Arterial Hypertension

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

Die Leukotriene, superaktive, an Allergie und Entzündung beteiligte Wirkstoffe

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Leukotriene B4: A highly potent and stereospecific factor stimulating migration of polymorphonuclear leukocytes

Cited by 137 publications

References 10 publications

Role of Oxidized Lipids in Pulmonary Arterial Hypertension

Role of Oxidized Lipids in Pulmonary Arterial Hypertension

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

Die Leukotriene, superaktive, an Allergie und Entzündung beteiligte Wirkstoffe

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Leukotriene B₄: A highly potent and stereospecific factor stimulating migration of polymorphonuclear leukocytes

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