Role of protein kinases in stimulation of human polymorphonuclear leukocyte oxidative metabolism by various agonists. Differential effects of a novel protein kinase inhibitor.

Gerard, Craig; McPhail, Linda C.; Marfat, Anthony; Stimler-Gerard, Norma P.; Bass, David; McCall, Charles E.

doi:10.1172/jci112302

Cited by 214 publications

(58 citation statements)

References 31 publications

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“…All of the reported agonist and antagonist properties of PMA have been shown to be inhibited by protein kinase C inhibitors [23,26,27]. There are two possible explanations for this result.…”

Section: Methodsmentioning

confidence: 93%

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Cell alkalinization is not necessary and increased sodium influx is not sufficient for stimulated superoxide production

et al. 1986

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Preincubation of rabbit neutrophils for 5 min with the protein kinase C inhibitor H7 causes inhibition of the rise in intracellular pH but not the increase in Na+ influx or stimulated oxidative burst produced by the chemotactic factor formyl-methionyl-leucyl-phenylalanine.On the other hand, the stimulated superoxide production, but not the increase in Nat influx produced by phorbol 12-myristate 13-acetate, is inhibited by H7. The effect is more pronounced on the rate than the extent of the stimulated superoxide release. Furthermore, cell acidification produced by the phorbol ester but not by the chemotactic factor is decreased in the presence of H7. These results suggest that (i) most of the stimulated Na+ influx is not coupled to H+ efflux, (ii) in the case of the chemoattractant, the rise in intracellular pH is not necessary for stimulated superoxide production, (iii) the increase in Nat influx, in the case of the phorbol ester, is not sufficient for the stimulation of the oxidative burst, and (iv) the sources of the H+ responsible for the stimulated pH drop are the various metabolic activities of the cell, including NADPH oxidation and activation of the hexose monophosphate shunt. H7IonJIux Protein kinase C &peroxide

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Section: Methodsmentioning

confidence: 93%

“…In fact, a small but significant increase is commonly observed. Gerard et al [26] have very recently demonstrated that the stimulation by PMA of the oxidative metabolism of human neutrophils, but not by fMet-Leu-Phe, could be inhibited by an …”

Section: Methodsmentioning

confidence: 99%

Cell alkalinization is not necessary and increased sodium influx is not sufficient for stimulated superoxide production

et al. 1986

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“…However, the inhibitors which were used are known not to be specific for protein kinase C. Cl affects both protein kinase C and the cyclic AMP-dependent kinase, the K; for the former enzyme being-20 tM and for the latter, 3 tiM (Gerard et al, 1986) and the respective Ki values for H7 are 6 JAM and 3 JAM (Hidaka et al, 1984). The cyclic AMP-dependent kinase is known to inhibit neutrophil responses (Fantone & Kinnes, 1983).…”

Section: Discussionmentioning

confidence: 99%

Comparison of the effects of indomethacin, RHC80267 and R59022 on superoxide production by 1,oleoyl‐2,acetyl glycerol and A23187 in human neutrophils

Dale

Penfield

1987

British J Pharmacology

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Indomethacin (10−4 m) causes marked augmentation of O−2release from human neutrophils when these are stimulated by either 1,oleoyl‐2,acetylglycerol or the divalent cation ionophore, A23187, the concentration‐response curve for each agent being shifted to the left and the maximum response to each increased. The diacylglycerol kinase inhibitor, R59022 (10−5 m) has effects very similar to those of indomethacin on both the 1,oleoyl‐2,acetylglycerol‐induced and the A23187‐induced concentration‐response curves for O2‐ generation. The diacylglycerol lipase inhibitor, RHC80267 (10−5 m) on the other hand, has a similar effect to indomethacin on 1,oleoyl‐2,acetylglycerol‐induced O−2 generation but, unlike indomethacin, has no effect on A23187‐induced O−2 generation. Comparison of the effects of these three agents provides a clue to the locus of the action of indomethacin in increasing superoxide release, suggesting that it may act as a diacylglycerol kinase inhibitor. A component of diacylglycerol lipase inhibition may also be present. It is suggested that these results could have relevance for the use of indomethacin as an anti‐inflammatory agent in chronic rheumatoid diseases.

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“…inhibitors were reported to inhibit PMA-but not receptor mediated 02 -formation, suggesting that NADPH oxidase activation by FMLP may be independent of PKC [4,5]. Furthermore, PKC-independent activation of NADPH oxidase in cellfree systems was demonstrated by us and others [6,7].…”

mentioning

confidence: 94%

Stimulus-dependent inhibition of platelet aggregation by the protein kinase C inhibitors polymyxin B, H-7 and staurosporine

Schächtele¹,

Seifert

Oßwald³

1988

Biochemical and Biophysical Research Communications

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The effects of various protein kinase C (PKC) inhibitors on NADPH oxidase (NO) activation by the phorbol ester PMA and by the chemotactic peptide FMLP were studied. H-7 reduced the effects of both stimuli in human neutrophils (HN) and HL-60 cells by 13-63%. Polymyxin B did not inhibit NO activation by PMA and FMLP in HN and reduced the effects of both stimuli in HL-60 cells by 27-55%. Retinal and retinoic acid enhanced the effects of PMA and FMLP in HL-60 cells and of FMLP in HN up to 4.5-fold. In contrast, retinoic acid inhibited the effect of PMA in HN, In the presence of cytochalasin B, retinal inhibited the effect of FMLP in HN, whereas retinoic acid inhibited NO activation by FMLP in both cell types. The dual PKC/calmodulin inhibitors trifluoperazine and W-7 abolished NO activation by PMA and FMLP in HN and HL-60 cells. Thus, the effects of PKC inhibitors on NO activation exhibit (I) cell type specificity, (2) stimulus dependency and (3) no correlation with in vitro inhibition of PKC. Our results suggest that studies with PKC inhibitors presently available cannot clarify the role of PKC in NO activation. ~1988Ac~d .... Press, Inc.Human neutrophils possess an NADPH oxidase which catalyzes 0 2" formation and can be activated by cell-permeable diacylglycerol and PMA via PKC [I,2] and by the chemotactic peptide, FMLP [3]. The mechanism by which FMLP activates 0 2 -formation is not known. There is a debate concerning the involvement of PKC in cellular activation by FMLP [3]. In recent studies, certain PKC

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Role of protein kinases in stimulation of human polymorphonuclear leukocyte oxidative metabolism by various agonists. Differential effects of a novel protein kinase inhibitor.

Cited by 214 publications

References 31 publications

Cell alkalinization is not necessary and increased sodium influx is not sufficient for stimulated superoxide production

Cell alkalinization is not necessary and increased sodium influx is not sufficient for stimulated superoxide production

Comparison of the effects of indomethacin, RHC80267 and R59022 on superoxide production by 1,oleoyl‐2,acetyl glycerol and A23187 in human neutrophils

Stimulus-dependent inhibition of platelet aggregation by the protein kinase C inhibitors polymyxin B, H-7 and staurosporine

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