Lysophosphatidylcholine induces mast cell secretion and protein kinase C activation

Marquardt, Diana L.; Walker, Linda L.

doi:10.1016/0091-6749(91)90178-q

Cited by 29 publications

(18 citation statements)

References 21 publications

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“…Lyso PC is a potent mitogen and also activates PKC, a potent mediator of AP-1 activation. 15,16 Recent studies indicated that ox-LDL-induced MAPK activation in vascular smooth muscle is dependent on the activation of PKC. 17 Both protein tyrosine kinase (PTK) and PKC are involved in lysoPC-induced MAPK activation in mesangial cells.…”

Section: Discussionmentioning

confidence: 99%

Oxidized LDL induces transcription factor activator protein‐1 in rat mesangial cells

Wang

Zhou

et al. 2003

Cell Biochemistry & Function

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It has been shown that oxidized low-density lipoprotein (ox-LDL), through the activation of glomerular cells, stimulates pathobiological processes involved in monocyte infiltration into the mesangium. The underlying molecular mechanisms are not fully understood. The present study showed that ox-LDL strongly induced AP-1 binding activity in rat mesangial cells (RMCs) in a dose- and time-dependent manner, reaching the maximal activation at 250 microg ml(-1) within 24 h. The results from mobility shift assays and Western blotting analysis revealed that this AP-1 binding increase involved c-Jun, but not c-Fos. Moreover, this ox-LDL-increased AP-1 binding was inhibited by several protein kinase (PK) inhibitors: the protein kinase C (PKC) inhibitor Bisindolylmaleimide I, the cAMP-dependent PK (PKA) inhibitor H89, and the tyrosine PK (PTK) inhibitor genistein. Protein phosphorylation represents mitogen-activated protein kinase (MAPK) activity. Therefore, we examined the role of ox-LDL on the activation of mesangial cell JNK/SAPK, the only recognized protein kinase that catalyses phosphorylation of c-Jun. The incubation of mesangial cells with ox-LDL induced phosphorylation of JNK1/SAPK dose dependently, with the maximal response at 150 microg ml(-1). This study demonstrates that multiple kinase activities are involved in the mechanism of ox-LDL-induced AP-1 activation in mesangial cells, and ox-LDL stimulates AP-1 through JNK-c-Jun other than MEK-c-Fos signalling pathway.

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Section: Discussionmentioning

confidence: 99%

Oxidized LDL induces transcription factor activator protein‐1 in rat mesangial cells

Wang

Zhou

et al. 2003

Cell Biochemistry & Function

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“…This suggests that LPC is probably the most biologically relevant, at least with respect to cytotoxicity, of the three PL used in the current study. Aside from cytotoxic/cytolytic properties, the pro-inflammatory actions of LPC include induction of mast cell secretion [2], upregulation of the endothelial adhesion molecules, P-selectin and ICAM-1 [3], activation of protein kinase C [4] and PIP 3 kinase [5], as well as activation of superoxide production by neutrophils [5], as described in the present study. The vitamin E status of an individual may therefore be an important determinant of the reactivity of LPC.…”

Section: Discussionmentioning

confidence: 99%

“…Both LPC and PAF possess pro-inflammatory properties [1][2][3][4][5] compatible with a role for these bioactive PL in the immunopathogenesis of a wide variety of acute [6][7][8][9] and chronic inflammatory disorders of both infective and noninfective origin. These molecules appear to be particularly important as mediators of inflammatory conditions of the airways, including bronchial asthma [10][11][12].…”

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confidence: 99%

Vitamin E attenuates the injurious effects of bioactive phospholipids on human ciliated epitheliumin vitro

Feldman

Anderson²,

Theron³

et al. 2001

Eur Respir J

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Bioactive phospholipids (PL), particularly lysophosphatidylcholine (LPC), are being increasingly implicated in the pathogenesis of various acute and chronic inflammatory disorders, particularly those of the airways, while there is emerging evidence that vitamin E may function as a natural antagonist of these lipid mediators of inflammation. The aims of this study were to document the effects of vitamin E on the inhibition of ciliary beating and damage to structural integrity of human ciliated epithelium induced by the PL, platelet-activating factor (PAF), lyso-PAF and LPC in vitro in relation to the anti-oxidative and membrane-stabilizing properties of the vitamin.Ciliary beat frequency was measured by a phototransistor technique, and damage to structural integrity assessed by a visual-scoring index, while superoxide production by polymorphonuclear leukocytes and membrane-stabilizing potential were measured using lucigenin-enhanced chemiluminescence and haemolytic procedures, respectively.All three PL caused inhibition of ciliary beating and structural damage to human ciliated epithelium by membrane-directed cytotoxic mechanisms, which were potentiated by human polymorphonuclear leukocytes due to induction of oxidant-mediated injury. Both direct and phagocyte-inflicted epithelial injury was attenuated by vitamin E. In haemolytic and chemiluminescence assays, vitamin E neutralized both the membrane-destabilizing and pro-oxidative actions of all three PL, while spectrophotometric analysis of mixtures of vitamin E with PAF, lyso-PAF and LPC revealed alterations in peak intensity, as well as peak shifts, indicative of physicochemical interactions between the vitamin and the PL.Vitamin E status may be a determinant of susceptibility to phospholipid-mediated airway inflammation and damage.

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“…Apart from its pro-oxidative and cytotoxic properties, which are shared by PAF and LPAF, LPC also induces mast cell secretion by promoting influx of extracellular calcium (Marquardt & Walker, 1991), while exposure of respiratory epithelium to lysophospholipids and PAF is accompanied by ciliary dysfunction, cytotoxicity and impaired mucociliary clearance (Ganbo et al, 1991;Nieminen et al, 1991;Feldman et al, 1995). Although many of the pro-inflammatory activities of PAF are clearly receptor-mediated (Barnes, 1989;Zimmerman et al, 1992), some activities of this bioactive phospholipid, as well as those of LPC and LPAF, appear to be mediated by receptor-independent, membrane-disruptive mechanisms which may be amenable to pharmacological control by membrane-stabilizing agents.…”

Section: Discussionmentioning

confidence: 99%

Anti‐inflammatory, membrane‐stabilizing interactions of salmeterol with human neutrophils in vitro

Anderson

Feldman

Theron

et al. 1996

British J Pharmacology

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1 We have investigated the effects of salmeterol (0.3-50 yM) on several pro-inflammatory activities of human neutrophils in vitro. 2 Oxidant production by FMLP-and calcium ionophore (A23187)-activated neutrophils was particularly sensitive to inhibition by low concentrations (0.3-3 IIM) of salmeterol, while the responses of phorbol myristate acetate-and opsonised zymosan-stimulated cells were affected only by higher concentrations (3-50 yM) of the drug. At these concentrations salmeterol is not cytotoxic, nor does it act as a scavenger of superoxide. 3 These anti-oxidative interactions of salmeterol with neutrophils were insensitive to propranolol but could be eliminated by washing the cells, or by pretreatment with low concentrations (1-2 uM) of the pro-oxidative, membrane-destabilizing phospholipids, lysophosphatidylcholine (LPC), platelet activating factor (PAF) and lysoPAF (LPAF). 4 At concentrations of 6.25-50 yM salmeterol interfered with several other activities of stimulated neutrophils, including intracellular calcium fluxes, phospholipase A2 activity and synthesis of PAF. 5 In an assay of membrane-stabilizing activity, salmeterol (25 and 50 Mm) neutralized the haemolytic action of LPC, PAF and LPAF. 6 Of the other commonly used /32-adrenoceptor agonists, fenoterol, and formoterol, but not salbutamol, caused moderate inhibition of neutrophil oxidant generation by a superoxide-scavenging mechanism. However, unlike salmeterol, these agents possessed only weak membrane stabilizing properties. 7 We conclude that salmeterol antagonizes the pro-inflammatory, pro-oxidative activity of several bioactive lipids implicated in the pathogenesis of bronchial asthma, by a mechanism related to the membrane-stabilizing, rather than to the f2-agonist properties of this agent.

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Lysophosphatidylcholine induces mast cell secretion and protein kinase C activation

Cited by 29 publications

References 21 publications

Oxidized LDL induces transcription factor activator protein‐1 in rat mesangial cells

Oxidized LDL induces transcription factor activator protein‐1 in rat mesangial cells

Vitamin E attenuates the injurious effects of bioactive phospholipids on human ciliated epitheliumin vitro

Anti‐inflammatory, membrane‐stabilizing interactions of salmeterol with human neutrophils in vitro

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