The Effect of a Protein Kinase C Inhibitor, H-7, on Human Neutrophil Oxidative Burst and Degranulation

Berkow, Roger L.; Dodson, Robert W.; Kraft, Andrew S.

doi:10.1002/jlb.41.5.441

Cited by 77 publications

(19 citation statements)

References 29 publications

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“…Together with the present results, this indicates, that PKC activity plays a minor role in agonist-induced EPO release, which is in agreement with interpretations based on experiments with H-7 or C-l in neutrophils (50)(51)(52). The unexpected, staurosporine-dependent increase in EPO release seems to be decoupled from PKC-mediated protein phosphorylation.…”

Section: (Pkc) (45-49)supporting

confidence: 93%

Shape changes, exocytosis, and cytosolic free calcium changes in stimulated human eosinophils.

Kernen¹,

Wymann²,

Tscharner³

et al. 1991

J. Clin. Invest.

108

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Essentially pure preparations of normal density eosinophils obtained from patients with hypereosinophilic syndrome (HES) were stimulated with complement factor 5a (C5a), platelet-activating factor (PAF), FMLP and neutrophil-activating peptide (NAP-1/IL-8). Three responses were studied, the transient rise in cytosolic free calcium concentration (ICa2+j (derived from indo-1 fluorescence), shape changes (measured by laser turbidimetry), and exocytosis of eosinophil peroxidase (EPO) (assessed by H202/luminol-dependent chemiluminescence). Responses were obtained with all four agonists, but C5a and PAF were by far more potent than FMLP and NAP-1/IL-8, which induced only minor effects. Pretreatment of the cells with pertussis toxin attenuated ICa2+h changes, EPO release and, to a lesser extent, shape changes, indicating that GTP-binding proteins of Gi-type are involved in receptor-dependent signal transduction processes leading to these responses. A clear dissociation was observed in the control of the shape change response and EPO exocytosis. The shape change was not affected by Ca2' depletion or treatment with the protein kinase inhibitor staurosporine, but exocytosis was prevented by Ca2' depletion and markedly enhanced by staurosporine. The activation of the contractile system, leading to shape changes and motility, thus appears to be independent of the classical signal transduction pathway involving phospholipase C, a [Ca2j11 rise and protein kinase C activation. Exocytosis is, as expected, CIO+ dependent and appears to be under a negative control involving protein phosphorylations. (J. Clin. Invest.

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Section: (Pkc) (45-49)supporting

confidence: 93%

Shape changes, exocytosis, and cytosolic free calcium changes in stimulated human eosinophils.

Kernen¹,

Wymann²,

Tscharner³

et al. 1991

J. Clin. Invest.

108

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“…In agreement with previous studies, we found that H-7 and polymyxin B did not substantially inhibit receptor-mediated activation processes in neutrophils [5,6]. However, these compounds substantially inhibited FMLP-induced 02 -formation in HL-60 cells.…”

Section: Discussionsupporting

confidence: 93%

“…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%

Studies with protein kinase C inhibitors presently available cannot elucidate the role of protein kinase C in the activation of NADPH oxidase

Seifert

Schächtele²

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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“…The involvement of PKC in the respiratory burst in neutrophils is somewhat contradictory. Some groups reported no inhibition by PKC inhibitor for neutrophil superoxide generation stimulated by fMLP [42,43]. Others demonstrated a PKC-dependent mechanism of fMLPstimulated superoxide generation in neutrophils [44].…”

Section: Discussionmentioning

confidence: 99%

Trp-Lys-Tyr-Met-Val-D-Met stimulates superoxide generation and killing of Staphylococcus aureus via phospholipase D activation in human monocytes

Bae

Kim

et al. 1999

Journal of Leukocyte Biology

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The Effect of a Protein Kinase C Inhibitor, H-7, on Human Neutrophil Oxidative Burst and Degranulation

Cited by 77 publications

References 29 publications

Shape changes, exocytosis, and cytosolic free calcium changes in stimulated human eosinophils.

Shape changes, exocytosis, and cytosolic free calcium changes in stimulated human eosinophils.

Studies with protein kinase C inhibitors presently available cannot elucidate the role of protein kinase C in the activation of NADPH oxidase

Trp-Lys-Tyr-Met-Val-D-Met stimulates superoxide generation and killing of Staphylococcus aureus via phospholipase D activation in human monocytes

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