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. 1980 May;77(5):2533–2536. doi: 10.1073/pnas.77.5.2533

A phospholipase A2 inhibitory protein in rabbit neutrophils induced by glucocorticoids.

F Hirata, E Schiffmann, K Venkatasubramanian, D Salomon, J Axelrod
PMCID: PMC349435  PMID: 6930649

Abstract

When rabbit peritoneal neutrophils were treated with glucocorticoids, their chemotactic response to stimulation by the chemoattractant fMet-Leu-Phe was markedly reduced. Preincubation of cells with glucocorticoids also decreased phospholipase A2 (phosphatide 2-acylhydrolase, EC 3.1.1.4) activity in situ as measured by the release of [1-14C]arachidonic acid previously incorporated into phospholipids. The inhibitory potencies of glucocorticoids on phospholipase A2 activity correlated well with their anti-inflammatory activities and their abilities to bind to glucocorticoid receptors. Inhibitors of RNA and protein synthesis suppressed the inhibitory effect of glucocorticoids on phospholipase A2 activity. Digestion of the glucocorticoid-treated cells by Pronase overcame the inhibitory activity. Phospholipase A2 activity induced by Ca2+ ionophore A23187 was not affected by Pronase treatment. Gel filtration of proteins from neutrophil membranes labeled with [3H]lysine showed an induction of protein(s) (about 40,000 daltons) after glucocorticoid treatment. This protein inhibited a partially purified pancreatic phospholipase A2 and reduced the peptide-initiated chemotactic response of neutrophils.

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Selected References

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

  1. Baxter J. D., Tomkins G. M. Specific cytoplasmic glucocorticoid hormone receptors in hepatoma tissue culture cells. Proc Natl Acad Sci U S A. 1971 May;68(5):932–937. doi: 10.1073/pnas.68.5.932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Danon A., Assouline G. Inhibition of prostaglandin biosynthesis by corticosteroids requires RNA and protein synthesis. Nature. 1978 Jun 15;273(5663):552–554. doi: 10.1038/273552a0. [DOI] [PubMed] [Google Scholar]
  3. Fant M. E., Harbison R. D., Harrison R. W. Glucocorticoid uptake into human placental membrane vesicles. J Biol Chem. 1979 Jul 25;254(14):6218–6221. [PubMed] [Google Scholar]
  4. Flower R. J., Blackwell G. J. Anti-inflammatory steroids induce biosynthesis of a phospholipase A2 inhibitor which prevents prostaglandin generation. Nature. 1979 Mar 29;278(5703):456–459. doi: 10.1038/278456a0. [DOI] [PubMed] [Google Scholar]
  5. Gelehrter T. D., Tomkins G. M. The role of RNA in the hormonal induction of tyrosine aminotransferase in mammalian cells in tissue culture. J Mol Biol. 1967 Oct 14;29(1):59–76. doi: 10.1016/0022-2836(67)90181-7. [DOI] [PubMed] [Google Scholar]
  6. Hirata F., Axelrod J., Crews F. T. Concanavalin A stimulates phospholipid methylation and phosphatidylserine decarboxylation in rat mast cells. Proc Natl Acad Sci U S A. 1979 Oct;76(10):4813–4816. doi: 10.1073/pnas.76.10.4813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hirata F., Corcoran B. A., Venkatasubramanian K., Schiffmann E., Axelrod J. Chemoattractants stimulate degradation of methylated phospholipids and release of arachidonic acid in rabbit leukocytes. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2640–2643. doi: 10.1073/pnas.76.6.2640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hirata F., Toyoshima S., Axelrod J., Waxdal M. J. Phospholipid methylation: a biochemical signal modulating lymphocyte mitogenesis. Proc Natl Acad Sci U S A. 1980 Feb;77(2):862–865. doi: 10.1073/pnas.77.2.862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Knapp H. R., Oelz O., Roberts L. J., Sweetman B. J., Oates J. A., Reed P. W. Ionophores stimulate prostaglandin and thromboxane biosynthesis. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4251–4255. doi: 10.1073/pnas.74.10.4251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mallorga P., Tallman J. F., Henneberry R. C., Hirata F., Strittmatter W. T., Axelrod J. Mepacrine blocks beta-adrenergic agonist-induced desensitization in astrocytoma cells. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1341–1345. doi: 10.1073/pnas.77.3.1341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Neifeld J. P., Lippman M. E., Tormey D. C. Steroid hormone receptors in normal human lymphocytes. Induction of glucocorticoid receptor activity by phytohemagglutinin stimulation. J Biol Chem. 1977 May 10;252(9):2972–2977. [PubMed] [Google Scholar]
  12. Peterkofsky B., Tomkins G. M. Evidence for the steroid-induced accumulation of tyrosine-aminotransferase messenger RNA in the absence of protein synthesis. Proc Natl Acad Sci U S A. 1968 May;60(1):222–228. doi: 10.1073/pnas.60.1.222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Salomon D. S., Vistica D. T. Steroid receptors and steroid response in cultured L1210 murine leukemia cells. Mol Cell Endocrinol. 1979 Jan;13(1):55–71. doi: 10.1016/0303-7207(79)90076-5. [DOI] [PubMed] [Google Scholar]
  14. Ward P. A. The chemosuppression of chemotaxis. J Exp Med. 1966 Aug 1;124(2):209–226. doi: 10.1084/jem.124.2.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Werb Z. Biochemical actions of glucocorticoids on macrophages in culture. Specific inhibition of elastase, collagenase, and plasminogen activator secretion and effects on other metabolic functions. J Exp Med. 1978 Jun 1;147(6):1695–1712. doi: 10.1084/jem.147.6.1695. [DOI] [PMC free article] [PubMed] [Google Scholar]

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