Functional activity of enucleated human polymorphonuclear leukocytes.

Roos, Dirk; Voetman, AA; Meerhof, LJ

doi:10.1083/jcb.97.2.368

Cited by 207 publications

(117 citation statements)

References 36 publications

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“…The neutrophil's cytoplasm is sufficient to rapidly process and act on membrane receptor ligation information, as exemplified by the intact signaling and functional capacities of enucleated cytoplasts (e.g., ref. 32). Because neutrophils often function in anoxygenic environments, it is not surprising that their main source of energy is anaerobic glycolysis (33).…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Dissipative metabolic patterns respond during neutrophil transmembrane signaling

Petty

Kindzelskii

2001

Proc. Natl. Acad. Sci. U.S.A.

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Self-organization is a common theme in biology. One mechanism of self-organization is the creation of chemical patterns by the diffusion of chemical reactants and their nonlinear interactions. We have recently observed sustained unidirectional traveling chemical redox [NAD(P)H ؊ NAD(P) ؉ ] waves within living polarized neutrophils. The present study shows that an intracellular metabolic wave responds to formyl peptide receptor agonists, but not antagonists, by splitting into two waves traveling in opposite directions along a cell's long axis. Similar effects were noted with other neutrophilactivating substances. Moreover, when cells were exposed to an N-formyl-methionyl-leucyl-phenylalanine (FMLP) gradient whose source was perpendicular to the cell's long axis, cell metabolism was locally perturbed with reorientation of the pattern in a direction perpendicular to the initial cellular axis. Thus, extracellular activating signals and the signals' spatial cues are translated into distinct intracellular dissipative structures.cell polarity ͉ nonequilibrium thermodynamics ͉ chemotaxis L iving cells continuously exchange matter and energy with their environment; they are open thermodynamic systems far from equilibrium (1, 2). Nonequilibrium conditions permit the appearance of dissipative structures, such as chemical concentration oscillations and chemical patterns. Dissipative structures use some of the energy absorbed from the environment to create order in a system (2). Chemical oscillators and chemical wave propagation, which do not violate the Second Law of Thermodynamics because they occur far from equilibrium, are well known in physical chemistry (2-4). Temporal oscillations in NAD(P)H (NADH ϩ NADPH) autofluorescence have been observed in living cells (5), including macrophages, monocytes, and neutrophils (6-8). These oscillations are the result of feedback activation and inhibition of glycolytic enzymes, especially phosphofructokinase (5, 9). For example, phosphofructokinase is activated by its proximal product, ADP, and inhibited by its substrate and distal product, ATP. Both temporal oscillations in NADH concentration and traveling NADH waves have been observed in macroscopic whole cell extracts (9-12). Theoretical studies have predicted the existence and properties of spatial glycolytic patterns in eukaryotic cells (13)(14)(15)(16)(17)(18). This has been recently confirmed by our group for NAD(P)H and pH (19). The present study tests the hypothesis that metabolic waves in living cells respond to extracellular signals. To observe these dissipative structures, we imaged microscopically NAD(P)H autofluorescence. We now report changes in the physical properties of traveling NAD(P)H waves in neutrophils during activation and signaling that reflect environmental orientational cues. These metabolic patterns are consistent with the ideas of Turing, Prigogine, Hess, and others concerning the potential role of dissipative chemical structures in biological function. Cells. Human peripheral blood neutrophils were purifi...

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Dissipative metabolic patterns respond during neutrophil transmembrane signaling

Petty

Kindzelskii

2001

Proc. Natl. Acad. Sci. U.S.A.

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“…Cytoplasts-Enucleated PMN cytoplasts were prepared according to the method of Roos et al (37). Briefly, PMNs were resuspended in 4.5 ml of 12.5% Ficoll containing 20 M cytochalasin B and warmed at 37°C for 5 min before being layered onto a prewarmed step gradient consisting of 4.5 ml of 16% layered on top of 4.5 ml of 25% Ficoll, each containing 20 M cytochalasin B.…”

Section: Methodsmentioning

confidence: 99%

Priming of the Neutrophil Respiratory Burst Involves p38 Mitogen-activated Protein Kinase-dependent Exocytosis of Flavocytochrome b 558-containing Granules

Ward¹,

Nakamura²,

McLeish³

2000

Journal of Biological Chemistry

150

155

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The respiratory burst of human neutrophils is primed by a number of pro-inflammatory stimuli, including tumor necrosis factor-␣ (TNF␣) and lipopolysaccharide (LPS); however, the mechanism of priming remains unknown. LPS has been shown previously to increase membrane expression of flavocytochrome b 558 , a component of the NADPH oxidase. This study shows that TNF␣ also increases membrane expression of flavocytochrome b 558 . Mitogen-activated protein kinase (MAPK) modules have been implicated in the action of priming agents. Pharmacologic inhibitors of MAPKs, SB203580 and PD098059, revealed that priming of the respiratory burst and up-regulation of flavocytochrome b 558 are dependent on p38 MAPK but not on extracellular-signal regulated kinase (ERK). TNF␣ and LPS primed respiratory burst activity and increased membrane expression of CD35 and CD66b, specific markers of secretory vesicles and specific granules that contain flavocytochrome b 558 , with similar time courses and concentration dependences. These processes also required p38 MAPK but were independent of ERK. TNF␣ failed to prime respiratory burst activity or to increase membrane CD35 expression in enucleated neutrophil cytoplasts. These data suggest that one mechanism by which TNF␣ and LPS prime neutrophil respiratory burst activity is by increasing membrane expression of flavocytochrome b 558 through exocytosis of intracellular granules in a process regulated by p38 MAPK.

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“…Thymosin b4 was assumed equimolar with actin, consistent with its concentrations in most cells 12,20,39,44,47 and with its function as the major sequestering protein. 23,48 Measurements of the concentration of profilin in cells range from 5 lM in chick brain 12 to 55 lM in platelets.…”

Section: Parameter Choicesmentioning

confidence: 99%

Relationships between Actin Regulatory Mechanisms and Measurable State Variables

Bindschadler

McGrath

2007

Ann Biomed Eng

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Abstract-In this report we extend our recent mathematical formulation of the actin cycle model [Bindschadler et al. Biophys. J. 86 (2004) 2720] to predict the influence of key regulatory mechanisms on network-scale state variables estimable in live cell experiments. Specifically, we examine the influence of regulation by cofilin, profilin, capping protein and proteins that adjust filament number through nucleation and/or filament severing, on the higher order variables of average filament length, polymer fraction, and filament turnover rate. Importantly, we find that severing/ nucleation, the acceleration of ADP-subunit disassembly by cofilin, and the catalytic and shuttle functions of profilin have Ôsignature' effects on the higher order state variables. In this way, measurement of the state variables in live cells can allow inference of regulatory mechanism(s) underlying changes in cell state. Our results compare favorably to published data for endothelial cells undergoing a transition from non-motile confluent cells to highly motile subconfluent cells. The extension of our model to higher order state variables allows us to investigate other important issues such as the distinction between basic and higher order measures of filament dynamics, the influence of thymosin b4 on network state variables, the interplay between thymosin b4 and profilin, and the synergystic effects of cofilin and profilin.

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Functional activity of enucleated human polymorphonuclear leukocytes.

Cited by 207 publications

References 36 publications

RETRACTED: Dissipative metabolic patterns respond during neutrophil transmembrane signaling

RETRACTED: Dissipative metabolic patterns respond during neutrophil transmembrane signaling

Priming of the Neutrophil Respiratory Burst Involves p38 Mitogen-activated Protein Kinase-dependent Exocytosis of Flavocytochrome b 558-containing Granules

Relationships between Actin Regulatory Mechanisms and Measurable State Variables

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