Increased LTB4 Metabolites and PGD2 In BAL Fluid after Methacholine Challenge in Asthmatic Subjects

Nowak, Dennis; Grimminger, Friedrich; Jörres, RA; Oldigs, M.; Rabe, Klaus F.; Seeger, W.; Magnussen, H

doi:10.1016/s0012-3692(16)47465-9

Chest

1993

DOI: 10.1016/s0012-3692(16)47465-9

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Increased LTB4 Metabolites and PGD2 In BAL Fluid after Methacholine Challenge in Asthmatic Subjects

Dennis Nowak¹,

Friedrich Grimminger²,

RA Jörres³

et al.

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Cited by 18 publications

(26 citation statements)

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“…Levels of prostaglandins and leukotrienes are increased in the airways of asthmatics and patients with COPD and have been measured in their exhaled breath, induced sputum, and bronchoalveolar lavage fluid (39,44,46,51,60,65). Furthermore, both in vivo and in vitro studies have shown eicosanoids to be important in airway remodeling.…”

mentioning

confidence: 99%

Prostaglandins but not leukotrienes alter extracellular matrix protein deposition and cytokine release in primary human airway smooth muscle cells and fibroblasts

Burgess

Brock

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Prostaglandins but not leukotrienes alter extracellular matrix protein deposition and cytokine release in primary human airway smooth muscle cells and fibroblasts. Am J Physiol Lung Cell Mol Physiol 303: L239-L250, 2012. First published May 25, 2012 doi:10.1152/ajplung.00097.2012.-Eicosanoids are lipid-signaling mediators released by many cells in response to various stimuli. Increasing evidence suggests that eicosanoids such as leukotrienes and prostaglandins (PGs) may directly mediate remodeling. In this study, we assessed whether these substances could alter extracellular matrix (ECM) proteins and the inflammatory profiles of primary human airway smooth muscle cells (ASM) and fibroblasts. PGE 2 decreased both fibronectin and tenascin C in fibroblasts but only fibronectin in ASM. PGD 2 decreased both fibronectin and tenascin C in both ASM and fibroblasts, whereas PGF 2␣ had no effect on ECM deposition. The selective PGI2 analog, MRE-269, decreased fibronectin but not tenascin C in both cell types. All the PGs increased IL-6 and IL-8 release in a dose-dependent manner in ASM and fibroblasts. Changes in ECM deposition and cytokine release induced by prostaglandins in both ASM and fibroblasts were independent of an effect on cell number. Neither the acute nor repeated stimulation with leukotrienes had an effect on the deposition of ECM proteins or cytokine release from ASM or fibroblasts. We concluded that, collectively, these results provide evidence that PGs may contribute to ECM remodeling to a greater extent than leukotrienes in airway cells.

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mentioning

confidence: 99%

Prostaglandins but not leukotrienes alter extracellular matrix protein deposition and cytokine release in primary human airway smooth muscle cells and fibroblasts

Burgess

Brock

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…We and others have recently found that the CC chemokine eotaxin, the most potent, in keeping with its high affinity for CCR3 (4), activates ERK1/2 and p38 MAPK in eosinophils, and that these kinases are indispensable for eosinophil chemotaxis (5,6). PGD 2 is a major arachidonic acid metabolite mainly released by Ag-activated mast cells (7), and a large amount of PGD 2 is generated in the asthmatic lung (8,9). PGD 2 directly acts through the DP1, and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), 4 which has been recently cloned as a Th2-selective surface molecule distinguished from Th1 cells (10).…”

mentioning

confidence: 99%

Physiological Levels of 15-Deoxy-Δ12,14-Prostaglandin J2 Prime Eotaxin-Induced Chemotaxis on Human Eosinophils through Peroxisome Proliferator-Activated Receptor-γ Ligation

Kobayashi

Ueki

Mahemuti

et al. 2005

The Journal of Immunology

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15-Deoxy-Δ12,14-PGJ2 (15d-PGJ2), mainly produced by mast cells, is known as a potent lipid mediator derived from PGD2 in vivo. 15d-PGJ2 was thought to exert its effects on cells exclusively through peroxisome proliferator-activated receptor-γ (PPARγ) and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), which are both expressed on human eosinophils. However, the physiological role of 15d-PGJ2 remains unclear, because the concentration generated in vivo is generally much lower than that required for its biological functions. In the present study we found that low concentrations (picomolar to low nanomolar) of 15d-PGJ2 and a synthetic PPARγ agonist markedly enhanced the eosinophil chemotaxis toward eotaxin, and the effect was decreased in a dose-dependent manner. Moreover, at a low concentration (10−10 M), 15d-PGJ2 and troglitazone primed eotaxin-induced shape change and actin polymerization. These priming effects were completely reversed by a specific PPARγ antagonist, but were not mimicked by CRTH2 agonist 13,14-dihydro-15-keto-PGD2, suggesting that the effects were mediated through PPARγ ligation. The effect exerted by 15d-PGJ2 parallels the enhancement of Ca2+ influx, but is not associated with the ERK, p38 MAPK, and NF-κB pathways. Furthermore, the time course and treatment of eosinophils with actinomycin D, an inhibitor of gene transcription, indicated that the transcription-independent pathway had a role in this process. PPARγ might interact with an eotaxin-induced cytosolic signaling pathway, because PPARγ is located in the eosinophil cytosol. Taken together with current findings, these results suggest that under physiological conditions, 15d-PGJ2 contributes to allergic inflammation through PPARγ, which plays a role as a biphasic regulator of immune response.

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“…Although many mediators of eosinophilia (e.g., IL-5, granulocyte-macrophage colony-stimulating factor [GM-CSF], and IL-3 [7]), eosinophil trafficking (RANTES, MIP-1␣ [3], and eotaxin [14]), and eosinophil activation (LTB4 [21]) have been shown to be expressed at high levels in the BAL fluid of asthmatic patients following allergen challenge, the mediators orchestrating eosinophilic chemotaxis and activation in TPE are largely unknown. The presence of eosinophilic granular proteins-eosinophil-derived neurotoxin (EDN), MBP, and eosinophilic cationic protein (ECP)-in the airways of patients with asthma (2, 15) has led to the hypothesis that these proteins play a role in the destruction of the bronchial epithelium (8); again, their exact role in TPE remains unexplored.…”

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Localized Eosinophil Degranulation Mediates Disease in Tropical Pulmonary Eosinophilia

et al. 2003

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To explore the mechanisms underlying the eosinophil-mediated inflammation of tropical pulmonary eosinophilia (TPE), bronchoalveolar lavage (BAL) fluid, serum, and supernatants from pulmonary and blood leukocytes (WBC) from patients with acute TPE (n ‫؍‬ 6) were compared with those obtained from healthy uninfected individuals (n ‫؍‬ 4) and from patients with asthma (n ‫؍‬ 4) or elephantiasis (n ‫؍‬ 5). Although there were no significant differences in the levels of interleukin-4 (IL-4), IL-5, IL-13, eotaxin, granulocyte-macrophage colony-stimulating factor, RANTES, or eosinophil cationic protein, there was a marked increase in eosinophil-derived neurotoxin (EDN) both systemically and in the lungs of individuals with TPE compared to each of the control groups (P < 0.02). Moreover, there was a compartmentalization of this response, with EDN levels being higher in the BAL fluid than in the serum (P < 0.02). Supernatants from WBC from either whole blood or BAL cells were examined for chemokines, cytokines, eosinophil degranulation products, and arachidonic acid metabolites. Of the many mediators examined-particularly those associated with eosinophil trafficking-only EDN (in BAL fluid and WBC) and MIP-1␣ (in WBC) levels were higher for TPE patients than for the non-TPE control groups (P < 0.02). These data suggest it is the eosinophilic granular protein EDN, an RNase capable of damaging the lung epithelium, that plays the most important role in the pathogenesis of TPE.Tropical pulmonary eosinophilia (TPE), an unusual manifestation of human lymphatic filarial infection, is characterized by an eosinophilic pulmonary inflammatory infiltrate and marked elevations of immunoglobulin E (IgE) and circulating eosinophils in the serum, all felt to be mediated by immunologic hyperreactivity to filarial parasites or their antigens. Although 129 million people worldwide are infected with lymphatic filariasis, Ͻ0.01% develop TPE (20). It is unclear what factors predispose patients to the rare, localized, and profound immune dysregulation associated with TPE.

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Increased LTB4 Metabolites and PGD2 In BAL Fluid after Methacholine Challenge in Asthmatic Subjects

Cited by 18 publications

References 0 publications

Prostaglandins but not leukotrienes alter extracellular matrix protein deposition and cytokine release in primary human airway smooth muscle cells and fibroblasts

Prostaglandins but not leukotrienes alter extracellular matrix protein deposition and cytokine release in primary human airway smooth muscle cells and fibroblasts

Physiological Levels of 15-Deoxy-Δ12,14-Prostaglandin J2 Prime Eotaxin-Induced Chemotaxis on Human Eosinophils through Peroxisome Proliferator-Activated Receptor-γ Ligation

Localized Eosinophil Degranulation Mediates Disease in Tropical Pulmonary Eosinophilia

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