Nonuniform Distribution of Ca2+ Uptake Sites within Human Neutrophils

Pettit, Elizabeth J.; Hallett, Maurice Bartlett

doi:10.1006/bbrc.2000.3954

Cited by 8 publications

(5 citation statements)

References 10 publications

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“…These are the plasma membrane Ca 2+ ‐ATPase, which is a Ca 2+ ‐efflux pump, and the endo‐membrane Ca 2 +‐ATPase which resequesters the cation into intracellular stores [23]. In activated neutrophils, these two Ca 2+ pumps appear to contribute more or less equally to the clearance of cytosolic Ca 2+ [24,25].…”

Section: Calcium Handling By Activated Neutrophilsmentioning

confidence: 99%

“…The plasma membrane Ca 2+ ‐ATPase of neutrophils is modulated by calmodulin, acidic phospholipids and polyunsaturated fatty acids which shift the pump to a higher‐affinity state for Ca 2+ , resulting in enhanced maximal velocity [26]. In the case of FMLP‐activated neutrophils, a dramatic and transient efflux of Ca 2+ immediately follows release of the cation from stores, proceeds over a 30‐s time course and results in discharge of about 50% of Ca 2+ mobilized from stores [24,25].…”

Section: Calcium Handling By Activated Neutrophilsmentioning

confidence: 99%

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Taming the neutrophil: calcium clearance and influx mechanisms as novel targets for pharmacological control

Tintinger

Steel

Anderson

2005

Clinical and Experimental Immunology

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SummaryNeutrophils are relatively insensitive to the anti-inflammatory actions of conventional chemotherapeutic agents, including corticosteroids, emphasizing the requirement for novel pharmacological strategies to control the potentially harmful proinflammatory activities of these cells. In the case of commonly-occurring inflammatory diseases of the airways, the neutrophil is the primary mediator of inflammation in conditions such as chronic obstructive pulmonary disease, cystic fibrosis, acute respiratory distress syndrome, bronchiectasis and non-eosinophilic bronchial asthma. Recent insights into the mechanisms utilized by neutrophils to restore Ca

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Section: Calcium Handling By Activated Neutrophilsmentioning

confidence: 99%

Section: Calcium Handling By Activated Neutrophilsmentioning

confidence: 99%

Taming the neutrophil: calcium clearance and influx mechanisms as novel targets for pharmacological control

Tintinger

Steel

Anderson

2005

Clinical and Experimental Immunology

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“…The calcium flux from the ER into the cytoplasm includes IP 3 -induced channel gating, calcium-induced calcium release, and transport of calcium into the ER via SERCA-pumps. This is motivated by the experimental observation that the system seems to play an active role in inflammatory calcium signaling (21)(22)(23). Therefore, we focus on this key regulatory step of calcium signaling in neutrophils.…”

Section: Introductionmentioning

confidence: 99%

Oscillatory NAD(P)H Waves and Calcium Oscillations in Neutrophils? A Modeling Study of Feasibility

Slaby¹,

Lebiedz²

2009

Biophysical Journal

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The group of Howard Petty has claimed exotic metabolic wave phenomena together with mutually phase-coupled NAD(P)H- and calcium-oscillations in human neutrophils. At least parts of these phenomena are highly doubtful due to extensive failure of reproducibility by several other groups and hints that unreliable data from the Petty lab are involved in publications concerning circular calcium waves. The aim of our theoretical spatiotemporal modeling approach is to propose a possible and plausible biochemical mechanism which would, in principle, be able to explain metabolic oscillations and wave phenomena in neutrophils. Our modeling suggests the possibility of a calcium-controlled glucose influx as a driving force of metabolic oscillations and a potential role of polarized cell geometry and differential enzyme distribution for various NAD(P)H wave phenomena. The modeling results are supposed to stimulate further controversial discussions of such phenomena and potential mechanisms and experimental efforts to finally clarify the existence and biochemical basis of any kind of temporal and spatiotemporal patterns of calcium signals and metabolic dynamics in human neutrophils. Independent of Petty's observations, they present a general feasibility study of such phenomena in cells.

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“…Although many of these pro‐inflammatory activities of PAF are believed to be achieved through receptor‐mediated increases in cytosolic Ca 2+ in target cells, relatively little is known about the sites (extracellular or intracellular) from which the cation is mobilized, or the mechanisms used by PAF‐activated cells to restore Ca 2+ homeostasis. In the case of neutrophils activated with chemoattractants such as N‐formyl‐ L ‐methionyl‐ L ‐leucyl‐ L ‐phenylalanine (FMLP), the plasma membrane and endo‐membrane Ca 2+ ‐ATPases, which are regulated by calmodulin and adenosine 3′,5′ cyclic monophosphate (cyclic AMP)‐dependent protein kinase respectively (Lagast et al ., 1984; Tao et al ., 1992), promote clearance of cytosolic Ca 2+ by efflux and resequestration of the cation (Anderson et al ., 1998; Pettit & Hallett, 2000). The efficiency of these Ca 2+ ‐clearance pumps is enhanced by the membrane depolarizing actions of NADPH oxidase which restrict the uptake of extracellular Ca 2+ (di virgilio et al ., 1987; Geiszt et al ., 1997; Tintinger et al ., 2001).…”

Section: Introductionmentioning

confidence: 99%

Dissociation of the PAF‐receptor from NADPH oxidase and adenylate cyclase in human neutrophils results in accelerated influx and delayed clearance of cytosolic calcium

Steel

Anderson

2002

British J Pharmacology

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1 The magnitude and duration of the abruptly occurring increases in cytosolic Ca 2+ in human neutrophils following activation with PAF (20 and 200 nM) and FMLP (1 mM), have been compared and related to alterations in NADPH oxidase activity, membrane potential and intracellular cyclic AMP. 2 Cytosolic Ca 2+ and membrane potential were measured by spectro¯uorimetry, transmembranē uxes of Ca 2+ by radiometric procedures, and NADPH oxidase activity and cyclic AMP by chemiluminescence and radioimmunoassay respectively. 3 Activation of neutrophils with both PAF (200 nM) and FMLP (1 mM) was accompanied by an abrupt increase in cytosolic Ca 2+ , which was of similar magnitude for each activator (393+9 and 378+17 nM respectively). Unlike FMLP-activated cells in which Ca 2+ was rapidly removed from the cytosol, peak levels of cytosolic Ca 2+ were sustained for longer (0.14+0.02 vs 1.16+0.04 min, P40.0001) and declined at a slower rate in PAF-treated neutrophils. 4 The prolonged elevation of cytosolic Ca 2+ in PAF-treated cells was due to accelerated storeoperated in¯ux of extracellular cation and was attenuated by dibutyryl cyclic AMP (4 mM), the Ca 2+ -chelator, EGTA (5 mM), and SKF 96365 (10 mM). In contrast to FMLP, basal levels of superoxide production and cyclic AMP were unaltered in PAF-activated neutrophils, while only moderate membrane depolarization was detected. 5 These observations demonstrate that mechanisms which restore Ca 2+ homeostasis to FMLPactivated neutrophils, viz. activation of NADPH oxidase and adenylate cyclase, are not operative in PAF-treated cells, presenting the potential hazard of Ca 2+ overload and hyperactivity.

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Nonuniform Distribution of Ca2+ Uptake Sites within Human Neutrophils

Cited by 8 publications

References 10 publications

Taming the neutrophil: calcium clearance and influx mechanisms as novel targets for pharmacological control

Taming the neutrophil: calcium clearance and influx mechanisms as novel targets for pharmacological control

Oscillatory NAD(P)H Waves and Calcium Oscillations in Neutrophils? A Modeling Study of Feasibility

Dissociation of the PAF‐receptor from NADPH oxidase and adenylate cyclase in human neutrophils results in accelerated influx and delayed clearance of cytosolic calcium

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