Phorbol 12-myristate 13-acetate activates rabbit neutrophils without an apparent rise in the level of intracellular free calcium

Sha'afi, R.I.; White, John R.; Molski, Thaddeus F.; Shefcyk, Jean; Volpi, M.; Naccache, Paul H.; Feinstein, Maurice B.

doi:10.1016/0006-291x(83)90828-8

Cited by 207 publications

(51 citation statements)

References 11 publications

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“…Several authors have shown that stimulation of neutrophils by phorbol esters or OAG causes inhibition of agonist-induced and A23187-induced increases in cytosolic Ca2" and speeds the rate of its return towards or below the prestimulation values (e.g. Sha'afi et al, 1983;Fujita et al, 1984;Schell-Frederick, 1984;Rickard & Sheterline, 1985;Naccache et al, 1985;Della Bianca et al, 1986), and we found this too (see Results).…”

Section: Discussionsupporting

confidence: 83%

“…One is that the inhibition of cell movement is caused by (a) enhanced cellular adhesiveness or (b) increased cell-cell adherence or (c) aggregation of the neutrophils, the last of which is a well recognized response to low doses of PMA (<10 nM) or diacylglycerols (Gallin et al, 1978;Sha'afi et al, 1983;O'Flaherty et al, 1985). However, we did not observe cell aggregates microscopically, and peripheral neutrophils aggregate less readily than elicited neutrophils, even when stirred (Bray et al, 1980).…”

Section: Discussioncontrasting

confidence: 58%

“…Estensen et al, 1974;SchellFrederick, 1974;Wright et al, 1977;Gallin et al, 1978;Lehmeyer et al, 1979;Sha'afi et al, 1983) and for OAG in human neutrophils (O'Flaherty et al, 1984). Exocytosis of specific granules occurs without mobilization of cytoplasmic calcium (Sha'afi et al, 1983), and is independent of extracellular calcium (Goldstein et al, 1974; these results). It is also unaffected by pretreatment with cytochalasin B (Lehmeyer et al, 1979), unlike degranulation responses induced by receptor-acting ligands.…”

Section: Discussionmentioning

confidence: 99%

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Divergent effects of co‐carcinogenic phorbol esters and a synthetic diacylglycerol on human neutrophil chemokinesis and granular enzyme secretion

Nourshargh

Hoult

1987

British J Pharmacology

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The effects of two co‐carcinogenic phorbol esters (phorbol myristate acetate (PMA) and phorbol dibutyrate (PDBu)) and a synthetic diacylglycerol (OAG, 1‐oleoyl‐2‐acetyl‐glycerol), which all stimulate protein kinase C, were compared with two inactive phorbol compounds (4α‐phorbol and 4α‐phorbol didecanoate (4α‐PDD)) on three functional properties of stimulated human polymorphonuclear leukocytes (PMNs): release of granular enzymes lysozyme and β‐glucuronidase, chemokinesis, and changes in cytoplasmic free calcium [Ca2+]i. PMA, PDBu and the diacylglycerol, OAG, all caused a dose‐dependent and slow (max by 15 min) release of small amounts of lysozyme with much less β‐glucuronidase and no release of cytoplasmic lactate dehydrogenase. Release was unaffected by removal of extracellular Ca2+. PMA, PDBu and OAG inhibited random movement of the cells, did not cause chemokinesis and induced a slow reduction in the basal [Ca2+]i, as measured by the quin‐2 method. PMA, PDBu and OAG increased the capacity of five independently‐acting stimulants (N‐formyl‐Met‐Leu‐Phe, leukotriene B4, C5a des‐Arg, platelet activating factor and A23187) to cause release of lysozyme and β‐glucuronidase but strongly inhibited PMN chemokinesis induced by the same five agents and reduced the stimulant‐induced increases in [Ca2+]i. PMA was always more potent than PDBu and much more potent than OAG in eliciting these stimulatory or inhibitory effects on human PMNs. In all tests, 4α‐phorbol and 4α‐PDD were inactive. The results confirm that stimulation of the diacylglycerol/protein kinase C system in human PMN, either by active phorbol esters or the synthetic diacylglycerol, causes bidirectional effects on human PMN function. In particular, activation of the C‐kinase causes inhibition of stimulated neutrophil motility, whereas the secretory functions of the cells are enhanced.

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Section: Discussionsupporting

confidence: 83%

Section: Discussioncontrasting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

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Divergent effects of co‐carcinogenic phorbol esters and a synthetic diacylglycerol on human neutrophil chemokinesis and granular enzyme secretion

Nourshargh

Hoult

1987

British J Pharmacology

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“…The stimulation of the NADPH oxidase by PKCs is closely related to their ability to phosphorylate p47 phox , one of the molecular components of this complex [127]. The selective secretion of specific granules induced by phorbol esters is itself likely the result of the lack of increases in the levels of cytoplasmic free calcium by this agonist [128] as the simultaneous addition of calcium ionophores results in complete neutrophil degranulation.…”

Section: Downstream Effector Pathwaysmentioning

confidence: 99%

Signalling in Neutrophils: A Retro Look

Naccache

2013

ISRN Physiology

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This review presents a summary of signalling events related to the activation of human polymorphonuclear neutrophils by a variety of soluble and particulate agonists. It is not intended as a comprehensive review of this vast field or as a presentation of the multiple new aspects of neutrophil functions that are being documented at an ever faster rate. Its aim is rather to focus on multiple aspects of major signalling pathways that, in the view of this reviewer, are currently shadowed by present trends and to provide the core evidence for their implication and the limitations of our present knowledge. More specifically, this review starts with cell surface receptors and some of their functional and biological properties and then moves on to downstream transducers (G proteins) and effectors (the phosphoinositide, tyrosine kinases, and cyclic nucleotide pathways). Classical second messengers (calcium, protein kinase C, polyphosphoinositides, and cyclic nucleotides) are emphasized. It is hoped that this presentation will not only remind present-day investigators of the central role these pathways play in the regulation of the functional responsiveness of neutrophils, but that it will also highlight some of the areas deserving additional investigation.

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“…However, there are certain problems and limitations inherent in experiments in which this stimulus is exclusively used. First, neutrophil responses to FMLP occur almost immediately after stimulation (20)(21)(22)(23) (24,(26)(27)(28)(29). Neutrophil responses to other metabolic stimuli are not similarly inhibited by pertussis toxin (24,(29)(30) (31,32).…”

Section: Introductionmentioning

confidence: 99%

Relationship of phosphatidylinositol bisphosphate hydrolysis to calcium mobilization and functional activation in fluoride-treated neutrophils.

English¹,

Debono²,

Gabig³

1987

J. Clin. Invest.

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Phorbol 12-myristate 13-acetate activates rabbit neutrophils without an apparent rise in the level of intracellular free calcium

Cited by 207 publications

References 11 publications

Divergent effects of co‐carcinogenic phorbol esters and a synthetic diacylglycerol on human neutrophil chemokinesis and granular enzyme secretion

Divergent effects of co‐carcinogenic phorbol esters and a synthetic diacylglycerol on human neutrophil chemokinesis and granular enzyme secretion

Signalling in Neutrophils: A Retro Look

Relationship of phosphatidylinositol bisphosphate hydrolysis to calcium mobilization and functional activation in fluoride-treated neutrophils.

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