The calcium signal and neutrophil activation

Krause, Karl‐Heinz; Campbell, Kevin P.; Welsh, Michael J.; Lew, Daniel Pablo

doi:10.1016/0009-9120(90)80030-m

Cited by 68 publications

(44 citation statements)

References 49 publications

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“…This suggests that AA does not compete with MC for binding at a common binding cleft of 5-LO but rather points to an uncompetitive mode of action. (Simchowitz and Spilberg, 1979;Krause et al, 1990;Mandeville and Maxfield, 1996). MC as well as S-MC concentration-dependently suppressed the increase in [Ca 2ϩ ] i in PMNLs evoked by the natural occurring agonist fMLP (100 nM).…”

Section: Resultsmentioning

confidence: 96%

“…Suppression of LT and PG synthesis by interfering with the 5-LO and COX pathways represent an efficient pharmacological approach for the treatment of inflammatory diseases (Funk, 2001). In addition, elevation of [Ca 2ϩ ] i causes release of proteases (e.g., leukocyte elastase or cathepsin G) and formation of ROS (Krause et al, 1990;Parekh and Penner, 1997), both which destroy invading particles but also damage cells and tissues of the host.…”

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confidence: 99%

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Identification of Molecular Targets of the Oligomeric Nonprenylated Acylphloroglucinols fromMyrtus communisand Their Implication as Anti-Inflammatory Compounds

Feißt

Franke²,

Appendino³

et al. 2005

J Pharmacol Exp Ther

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Myrtucommulone (MC) and semimyrtucommulone (S-MC) are unique oligomeric, nonprenylated acylphloroglucinols contained in the leaves of myrtle (Myrtus communis). Although extracts of myrtle have been traditionally used in folk medicine for the treatment of various disorders, studies addressing select cellular or molecular pharmacological properties of these extracts or specific ingredients thereof are rare. Here, we show for the first time that MC and S-MC potently suppress the biosynthesis of eicosanoids by direct inhibiting cyclooxygenase-1 and 5-lipoxygenase in vitro and in vivo at IC 50 values in the range of 1.8 to 29 M. Moreover, we show that MC and S-MC prevent the mobilization of Ca 2ϩ in polymorphonuclear leukocytes, mediated by G protein signaling pathways at IC 50 values of 0.55 and 4.5 M, respectively, and suppress the formation of reactive oxygen species and the release of elastase at comparable concentrations. The isobutyrophenone core of MC as well as S-MC was much less potent or even not active at all. In addition, MC or S-MC only partially inhibited peroxide formation or failed to block Ca 2ϩ mobilization and elastase release when polymorphonuclear leukocytes were challenged with ionomycin that circumvents G protein signaling for cell activation. We conclude that, in view of their ability to suppress typical proinflammatory cellular responses, the unique acylphloroglucinols MC and S-MC from myrtle may possess an anti-inflammatory potential, suggesting their therapeutic use for the treatment of diseases related to inflammation and allergy.Myrtle (Myrtus communis, Myrtaceae) is a Mediterranean shrub used as a culinary spice and as a folk medicine, for example, in the treatment of diabetes mellitus and as an antiseptic agent. In fact, myrtle extracts have been reported to possess antihyperglycemic (Elfellah et al., 1984;Sepici et al., 2004;Onal et al., 2005), antibacterial (Al-Saimary et al., 2002;Bonjar, 2004), and analgesic (Levesque and Lafont, 2000) properties. Recent reports have described antioxidant activities of different extracts of myrtle and certain ingredients thereof (Rosa et al., 2003;Hayder et al., 2004;Romani et al., 2004), implying potential as medicine for the treatment of diseases related to oxidative stress, including inflammatory disorders. Myrtle contains a great variety of compounds like bitter substances, ethereal oil, and tannic substances (elSissi and el-Ansary, 1967). In addition to these rather ubiquitous ingredients that are present in many plants, myrtle contains unique oligomeric, nonprenylated acylphloroglucinols such as myrtucommulone (MC) and semimyrtucommulone (S-MC) (Appendino et al., 2002), which are considered to be responsible for the antioxidative (Rosa et al., 2003)

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Section: Resultsmentioning

confidence: 96%

mentioning

confidence: 99%

Identification of Molecular Targets of the Oligomeric Nonprenylated Acylphloroglucinols fromMyrtus communisand Their Implication as Anti-Inflammatory Compounds

Feißt

Franke²,

Appendino³

et al. 2005

J Pharmacol Exp Ther

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“…The cytosolic free calcium concentration, [Ca 2ϩ ] i , in phagocytic cells is an important determinant of cellular activity and plays a central role in receptor-mediated intracellular signaling events [31]. Previously, PAF-induced changes in [Ca 2ϩ ] i have been shown for human [27] and rabbit [12] neutrophils.…”

Section: Calcium Response In Paf-treated Bovine Neutrophilsmentioning

confidence: 99%

Platelet-activating factor induces a concentration-dependent spectrum of functional responses in bovine neutrophils

Swain

Bunger

Sipes

et al. 1998

Journal of Leukocyte Biology

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We characterized the dose response of bovine neutrophils to platelet-activating factor (PAF) with respect to the following functions: calcium flux and membrane potential changes, actin polymerization, degranulation, and the production and/or priming of the oxidative burst. PAF at very low concentrations (10 -10 and 10 -9 M) caused changes in intracellular calcium and membrane potential in bovine neutrophils, whereas moderate PAF concentrations (H10 -7 M) resulted in increased actin polymerization. Degranulation responses to PAF were more complex: low concentrations (10 -9 M) caused secretory granule degranulation, moderate doses (H10 -7 M) caused specific granule degranulation, whereas azurophil degranulation only occurred at high (10 -5 M) PAF concentrations. Treatment of bovine neutrophils with PAF at concentrations H10 -7 M also caused up-regulation of the adhesion molecules Mac-1 and L-selectin. PAF stimulation resulted in a very weak [compared to phorbol myristate acetate (PMA)] oxidative burst in bovine neutrophils, and only at high (10 -6 M) concentrations. Unlike human neutrophils, bovine neutrophils were poorly primed by PAF treatment. Only high concentrations of PAF (10 -5 M) caused an increased rate of PMA-stimulated superoxide production, although lower doses of PAF did reduce the lag time preceding the PMA-induced oxidative burst. The overall pattern that can be inferred is that lower concentrations of PAF promote neutrophil sensitivity and interaction by selective degranulation, up-regulation of adhesion molecules, and increased actin polymerization. In contrast, higher PAF concentrations can promote, albeit weakly, more direct bactericidal responses, such as the release of reactive oxygen species and granule enzymes. The ability of PAF to modulate a graded response in bovine neutrophils would allow the cell to respond proportionally to the severity of a stimulus.

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“…The majority of formyl peptide-induced calcium up-regulation originates from extracellular calcium, 11 possibly entering through channels formed from Orai1 subunits. For example, production of bactericidal reactive oxygen species and GPCR-induced production of superoxide are partially dependent on extracellular calcium as it is sensitive to SOCE blockade by La 3ϩ .…”

Section: Introductionmentioning

confidence: 99%

Orai1 regulates intracellular calcium, arrest, and shape polarization during neutrophil recruitment in shear flow

Schaff

Dixit

Procyk

et al. 2010

Blood

101

121

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The calcium signal and neutrophil activation

Abstract: The cytosolic free calcium concentration, [

Cited by 68 publications

References 49 publications

Identification of Molecular Targets of the Oligomeric Nonprenylated Acylphloroglucinols fromMyrtus communisand Their Implication as Anti-Inflammatory Compounds

Identification of Molecular Targets of the Oligomeric Nonprenylated Acylphloroglucinols fromMyrtus communisand Their Implication as Anti-Inflammatory Compounds

Platelet-activating factor induces a concentration-dependent spectrum of functional responses in bovine neutrophils

Orai1 regulates intracellular calcium, arrest, and shape polarization during neutrophil recruitment in shear flow

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