Lysophosphatidic acid accelerates the development of human mast cells

Bagga, Savita; Price, Kursteen S.; Lin, Debby A.; Friend, Daniel S.; Austen, K. Frank; Boyce, Joshua A.

doi:10.1182/blood-2004-03-1166

Cited by 72 publications

(62 citation statements)

References 55 publications

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“…This stimulation was mediated through LPAR and PPARcdependent pathways to enhance proliferation and differentiation of human mast cells [17]. In addition, LPA was also reported to enhance osteogenic differentiation of human mesenchymal stem cells.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies also showed that stem cell differentiation is regulated through LPARs [16]. LPA accelerates proliferation and differentiation of human mast cells derived from cord blood through LPARs and peroxisome proliferator-activated receptor c (PPARc)-dependent pathways [17]. In addition, LPA induces osteoblastic differentiation from telomerase reverse transcriptase-overexpressed human mesenchymal stem cells through interplay of LPA 1 and LPA 4 [18].…”

Section: Introductionmentioning

confidence: 99%

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Lysophosphatidic Acid Induces Erythropoiesis through Activating Lysophosphatidic Acid Receptor 3

et al. 2011

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Lysophosphatidic acid (LPA), an extracellular lipid mediator, exerts multiple bioactivities through activating G protein-coupled receptors. LPA receptor 3 (LPA 3 ) is a member of the endothelial differentiation gene family, which regulates differentiation and development of the circulation system. However, the relationship among the LPA receptors (LPARs) and erythropoiesis is still not clear. In this study, we found that erythroblasts expressed both LPA 1 and LPA 3 , and erythropoietic defects were observed in zLPA 3 antisense morpholino oligonucleotide-injected zebrafish embryos. In human model, our results showed that LPA enhanced the erythropoiesis in the cord blood-derived human hematopoietic stem cells (hHSCs) with erythropoietin (EPO) addition in the plasma-free culture. When hHSCs were treated with Ki16425, an antagonist of LPA 1 and LPA 3 , erythropoietic process of hHSCs was also blocked, as detected by mRNA and protein expressions of CD71 and GlyA. In the knockdown study, we further demonstrated that specific knockdown of LPA 3 , not LPA 1 , blocked the erythropoiesis. The translocation of b-catenin into the nucleus, a downstream response of LPAR activation, was blocked by Ki16425 treatment. In addition, upregulation of erythropoiesis by LPA was also blocked by quercetin, an inhibitor of the b-catenin/ T-cell factor pathway. Furthermore, the enhancement of LPA on erythropoiesis was diminished by blocking c-Junactivated kinase/signal transducer and activator of transcription and phosphatidylinositol 3-kinase/AKT activation, the downstream signaling pathways of EPO receptor, suggested that LPA might play a synergistic role with EPO to regulate erythropoietic process. In conclusion, we first reported that LPA participates in EPO-dependent erythropoiesis through activating LPA 3 .

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lysophosphatidic Acid Induces Erythropoiesis through Activating Lysophosphatidic Acid Receptor 3

et al. 2011

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“…Lysophosphatidic acid (LPA), a bioactive lipid and major constituent of modified LDL, may be a potential candidate in this regard, as mast cells express several LPA receptors ( 17 ) through which LPA can affect mast cell function. Indeed, Bagga et al demonstrated that LPA accelerates human mast cell proliferation and differentiation via LPA 1/3 -and peroxisome proliferator-activated receptor ␥ -dependent pathways ( 18 ). In addition, LPA triggers the release of a wide range of proinfl ammatory chemokines such as macro phage infl ammatory protein-1 ␤ , IL-8, eotaxin, and monocyte chemoattractant protein (MCP)-1, which can attract infl ammatory cells to the arterial wall ( 19 ).…”

Section: Cell Culturementioning

confidence: 99%

Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation

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Jager

MacAleese

et al. 2013

Journal of Lipid Research

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Atherosclerotic plaque rupture is a leading cause of acute coronary syndromes, such as unstable angina and myocardial infarction ( 1 ). Infl ammatory cells are regarded as key players in the pathogenesis of plaque rupture ( 2, 3 ), and the mast cell, a potent infl ammatory cell, has been shown to accumulate in the rupture-prone shoulder region of human atheromas ( 4 ). Activated mast cells have been identifi ed in the adventitia of vulnerable and ruptured lesions in patients with myocardial infarction, and more importantly, their numbers and degree of activation were found to correlate with the incidence of plaque rupture and erosion ( 5 ). We previously demonstrated that systemic mast cell activation during atherogenesis leads to increased plaque progression in apoE defi cient mice ( 6 ), while others show that the absence of mast cells, and in particular mast cell-derived interleukin (IL)-6 and interferon (IFN)-␥ , attenuated atherosclerotic lesion development in low-density lipoprotein receptor-deficient (LDLr Ϫ / Ϫ ) mice ( 7 ). Moreover, focal activation of mast cells in the adventitia of advanced carotid artery plaques promoted macrophage apoptosis, microvascular leakage, de novo leukocyte infl ux, and the incidence of intraplaque hemorrhage. Mast cell stabilization by cromolyn was seen to prevent these pathophysiological events ( 6 ).Various pathways of mast cell activation have been demonstrated such as cross-linking of the high-affi nity Abstract Lysophosphatidic acid (LPA), a bioactive lysophospholipid, accumulates in the atherosclerotic plaque. It has the capacity to activate mast cells, which potentially exacerbates plaque progression. In this study, we thus aimed to investigate whether LPA contributes to plaque destabilization by modulating mast cell function. We here show by an imaging mass spectrometry approach that several LPA species are present in atherosclerotic plaques. Subsequently, we demonstrate that LPA is a potent mast cell activator which, unlike other triggers, favors release of tryptase. Local perivascular administration of LPA to an atherosclerotic carotid artery segment increases the activation status of perivascular mast cells and promotes intraplaque hemorrhage and macrophage recruitment without impacting plaque cell apoptosis. The mast cell stabilizer cromolyn could prevent intraplaque hemorrhage elicited by LPAmediated mast cell activation. Finally, the involvement of mast cells in these events was further emphasized by the lack of effect of perivascular LPA administration in mast cell defi cient animals. We demonstrate that increased accumulation of LPA in plaques induces perivascular mast cell activation and in this way contributes to plaque destabilization in vivo. This study points to local LPA availability as an important factor in atherosclerotic plaque stability. Press, February 10, 2013 DOI 10.1194 Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular infl ammation Abbreviations: apoE Ϫ / Ϫ , apolipoprotein E-defi...

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“…LPA induces various biological effects through these PTX-sensitive (G i / o ) or -insensitive (G 12/ 13 , G q ) G-proteins. Bagga et al reported that LPA-induced proliferation of mast cells was blocked by PTX; VPC-32179, a competitive antagonist of LPA 1 ; and LPA 2 (20). Renbäck et al reported LPA had a nociception-producting activity on sensory neurons through G i / o activation (21).…”

Section: Discussionmentioning

confidence: 99%

Lysophosphatidic Acid (LPA) Induces Plasma Exudation and Histamine Release in Mice via LPA Receptors

2006

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Abstract. Lysophosphatidic acid (LPA), the simplest of the water-soluble phospholipids, can evoke various biological responses. The present study examined the activity of LPA to induce plasma exudation and histamine release in mice. Plasma exudation was assessed by extravasation of Evans blue. Subcutaneous administration of LPA (1 -100 µg / site) led to increased plasma exudation in the skin. The LPA-induced plasma exudation was inhibited by ketotifen, a histamine H 1 -receptor antagonist, and diacylglycerol pyrophosphate (DGPP), a LPA 1 / LPA 3 -receptor antagonist. Moreover, pretreatment with pertussis toxin and DGPP inhibited the histamine release from peritoneal mast cells induced by LPA. These findings indicate that plasma exudation induced by LPA is mediated by histamine release from mast cells via LPA receptor(s), presumably LPA 1 and / or LPA 3 , coupled to G i / o proteins. Moreover, these findings point to a role of LPA in the pathomechanisms of various allergic disorders.

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Lysophosphatidic acid accelerates the development of human mast cells

Cited by 72 publications

References 55 publications

Lysophosphatidic Acid Induces Erythropoiesis through Activating Lysophosphatidic Acid Receptor 3

Lysophosphatidic Acid Induces Erythropoiesis through Activating Lysophosphatidic Acid Receptor 3

Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation

Lysophosphatidic Acid (LPA) Induces Plasma Exudation and Histamine Release in Mice via LPA Receptors

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