Skip to main content
PMC home page
Immunology logoLink to Immunology
. 1988 Apr;63(4):715–719.

Negative effect of a protein kinase C inhibitor (H-7) on human polymorphonuclear neutrophil locomotion.

M Gaudry 1, A Perianin 1, C Marquetty 1, J Hakim 1
PMCID: PMC1454805  PMID: 2835313

Abstract

The effects of 1-(5-isoquinoline sulphonyl)-2-methyl piperazine (H-7), a recently described inhibitor of Ca2+/phospholipid-dependent protein kinase (protein kinase C), were studied during under-agarose migration of human polymorphonuclear neutrophils (PMN) stimulated by various chemoattractants, in order to determine whether protein kinase C is involved in PMN locomotion. The effect of H-7 on the oxidative burst induced by phorbol 12-myristate 13-acetate or N-formyl-methionyl-leucyl-phenylalanine (FMLP) was also measured. Pre-incubation of PMN with H-7 concentrations ranging from 50 to 400 microM inhibited: (i) spontaneous PMN migration under agarose; (ii) the directed migration induced by activated serum, leukotriene B4 or FMLP; and (iii) the speed of the migration induced by FMLP. The inhibition by H-7 of FMLP-induced directed migration was less when FMLP was used at high concentrations which, in the absence of H-7, inhibit locomotion. H-7 depressed the oxidative burst induced by phorbol myristate acetate (PMA) but not that induced by FMLP. All the effects of H-7 on the oxidative burst and migration were reversed by washing PMN after H-7 treatment. These findings indicate that protein kinase C, inhibitable by H-7, is involved in a mechanism controlling the speed of PMN locomotion.

Full text

PDF
715

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berkow R. L., Dodson R. W., Kraft A. S. The effect of a protein kinase C inhibitor, H-7, on human neutrophil oxidative burst and degranulation. J Leukoc Biol. 1987 May;41(5):441–446. doi: 10.1002/jlb.41.5.441. [DOI] [PubMed] [Google Scholar]
  2. Castagna M., Takai Y., Kaibuchi K., Sano K., Kikkawa U., Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847–7851. [PubMed] [Google Scholar]
  3. Cohen H. J., Chovaniec M. E., Davies W. A. Activation of the guinea pig granulocyte NAD(P)H-dependent superoxide generating enzyme: localization in a plasma membrane enriched particle and kinetics of activation. Blood. 1980 Mar;55(3):355–363. [PubMed] [Google Scholar]
  4. Hidaka H., Inagaki M., Kawamoto S., Sasaki Y. Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C. Biochemistry. 1984 Oct 9;23(21):5036–5041. doi: 10.1021/bi00316a032. [DOI] [PubMed] [Google Scholar]
  5. Kaibuchi K., Takai Y., Sawamura M., Hoshijima M., Fujikura T., Nishizuka Y. Synergistic functions of protein phosphorylation and calcium mobilization in platelet activation. J Biol Chem. 1983 Jun 10;258(11):6701–6704. [PubMed] [Google Scholar]
  6. Katoh N., Wise B. C., Kuo J. F. Phosphorylation of cardiac troponin inhibitory subunit (troponin I) and tropomyosin-binding subunit (troponin T) by cardiac phospholipid-sensitive Ca2+-dependent protein kinase. Biochem J. 1983 Jan 1;209(1):189–195. doi: 10.1042/bj2090189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kawamoto S., Hidaka H. Ca2+-activated, phospholipid-dependent protein kinase catalyzes the phosphorylation of actin-binding proteins. Biochem Biophys Res Commun. 1984 Feb 14;118(3):736–742. doi: 10.1016/0006-291x(84)91456-6. [DOI] [PubMed] [Google Scholar]
  8. Nishihira J., McPhail L. C., O'Flaherty J. T. Stimulus-dependent mobilization of protein kinase C. Biochem Biophys Res Commun. 1986 Jan 29;134(2):587–594. doi: 10.1016/s0006-291x(86)80460-0. [DOI] [PubMed] [Google Scholar]
  9. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  10. Perianin A., Gougerot-Pocidalo M. A., Giroud J. P., Hakim J. Diclofenac binding to human polymorphonuclear neutrophils: effect on respiratory burst and N-formylated peptide binding. Biochem Pharmacol. 1987 Aug 15;36(16):2609–2615. doi: 10.1016/0006-2952(87)90539-9. [DOI] [PubMed] [Google Scholar]
  11. Perianin A., Gougerot-Pocidalo M. A., Giroud J. P., Hakim J. Diclofenac sodium, a negative chemokinetic factor for neutrophil locomotion. Biochem Pharmacol. 1985 Oct 1;34(19):3433–3438. doi: 10.1016/0006-2952(85)90714-2. [DOI] [PubMed] [Google Scholar]
  12. Perianin A., Labro M. T., Hakim J. Chemokinetic activity of N-formyl-methionyl-leucyl-phenylalanine on human neutrophils, and its modulation by phenylbutazone. Biochem Pharmacol. 1982 Oct 1;31(19):3071–3076. doi: 10.1016/0006-2952(82)90082-x. [DOI] [PubMed] [Google Scholar]
  13. Snyderman R., Pike M. C. Chemoattractant receptors on phagocytic cells. Annu Rev Immunol. 1984;2:257–281. doi: 10.1146/annurev.iy.02.040184.001353. [DOI] [PubMed] [Google Scholar]
  14. Snyderman R., Smith C. D., Verghese M. W. Model for leukocyte regulation by chemoattractant receptors: roles of a guanine nucleotide regulatory protein and polyphosphoinositide metabolism. J Leukoc Biol. 1986 Dec;40(6):785–800. doi: 10.1002/jlb.40.6.785. [DOI] [PubMed] [Google Scholar]
  15. Tauber A. I. Protein kinase C and the activation of the human neutrophil NADPH-oxidase. Blood. 1987 Mar;69(3):711–720. [PubMed] [Google Scholar]
  16. White J. R., Huang C. K., Hill J. M., Jr, Naccache P. H., Becker E. L., Sha'afi R. I. Effect of phorbol 12-myristate 13-acetate and its analogue 4 alpha-phorbol 12,13-didecanoate on protein phosphorylation and lysosomal enzyme release in rabbit neutrophils. J Biol Chem. 1984 Jul 10;259(13):8605–8611. [PubMed] [Google Scholar]
  17. Wolfson M., McPhail L. C., Nasrallah V. N., Snyderman R. Phorbol myristate acetate mediates redistribution of protein kinase C in human neutrophils: potential role in the activation of the respiratory burst enzyme. J Immunol. 1985 Sep;135(3):2057–2062. [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES