Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1979 Jun;76(6):2922–2926. doi: 10.1073/pnas.76.6.2922

Phospholipid methylation in macrophages is inhibited by chemotactic factors

Marilyn C Pike *,, Nicholas M Kredich ‡,§,, Ralph Snyderman *,‡,§,†,ǁ
PMCID: PMC383722  PMID: 288076

Abstract

Chemotaxis by human monocytes has been shown to require methylation mediated by S-adenosyl-L-methionine(AdoMet), but the specific transmethylation reaction necessary for this function was not elucidated. In an attempt to define the methylation requirement for chemotaxis, we examined the effect of chemotactic agonists and antagonists on protein carboxy-O-methylation of protein and methylation of phospholipid in guinea pig macrophages. Chemotactic agents tested over a wide dose and time range produced no alteration in carboxy-O-methylation. However, these agents did produce an effect on the methylation of phosphatidylethanolamine by macrophages. AdoMet-mediated phospholipid methylation was inhibited by as much as 73% by chemotactic factors, and there was excellent correlation (r = 0.99) between their concentrations for producing half-maximal chemotactic responses and for inhibiting phospholipid methylation. The inhibition of methylation by chemotactic factors was observed at all incubation times and could not be explained by an increased turnover of membrane phospholipid. Neither the chemotaxis antagonist fPhe-Met nor the nonchemotactic tripeptide Met-Met-Met significantly depressed phospholipid methylation. Immune phagocytosis by macrophages similarly did not alter phospholipid methylation. The chemotactic factors produced no alteration in total macrophage phospholipid synthesis or in the phospholipid methylation in a nonchemotactic cell type. The formation of newly methylated derivatives of phosphatidylethanolamine in macrophages was decreased by a biologically active dose of chemotactic factor. These findings indicate that chemotactic factors are capable of altering the methylation of phosphatidylethanolamine in chemotactically responsive cells. The inhibition of phospholipid methylation by chemotactic factors may be necessary for the translation of a chemotactic signal on the surface of the cell into directional cell movement.

Keywords: S-adenosyl-L-methionine, carboxy-O-methylation, phagocytosis, phosphatidylcholine, phosphatidylethanolamine

Full text

PDF
2922

Selected References

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

  1. Adler J. Chemotaxis in bacteria. Annu Rev Biochem. 1975;44:341–356. doi: 10.1146/annurev.bi.44.070175.002013. [DOI] [PubMed] [Google Scholar]
  2. Aswanikumar S., Corcoran B., Schiffmann E., Day A. R., Freer R. J., Showell H. J., Becker E. L. Demonstration of a receptor on rabbit neutrophils for chemotactic peptides. Biochem Biophys Res Commun. 1977 Jan 24;74(2):810–817. doi: 10.1016/0006-291x(77)90375-8. [DOI] [PubMed] [Google Scholar]
  3. Cantoni G. L. Biological methylation: selected aspects. Annu Rev Biochem. 1975;44:435–451. doi: 10.1146/annurev.bi.44.070175.002251. [DOI] [PubMed] [Google Scholar]
  4. Diliberto D. J., Jr, Veiveros O. H., Axelrod J. Subcellualr distribution of protein carboxymethylase and its endogenous substrates in the adrenal medulla: possible role in excitation-secretion coupling. Proc Natl Acad Sci U S A. 1976 Nov;73(11):4050–4054. doi: 10.1073/pnas.73.11.4050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Diliberto E. J., Jr, Axelrod J. Regional and subcellular distribution of protein carboxymethylase in brain and other tissues. J Neurochem. 1976 Jun;26(6):1159–1165. doi: 10.1111/j.1471-4159.1976.tb07001.x. [DOI] [PubMed] [Google Scholar]
  6. Hirata F., Axelrod J. Enzymatic synthesis and rapid translocation of phosphatidylcholine by two methyltransferases in erythrocyte membranes. Proc Natl Acad Sci U S A. 1978 May;75(5):2348–2352. doi: 10.1073/pnas.75.5.2348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hirata F., Viveros O. H., Diliberto E. J., Jr, Axelrod J. Identification and properties of two methyltransferases in conversion of phosphatidylethanolamine to phosphatidylcholine. Proc Natl Acad Sci U S A. 1978 Apr;75(4):1718–1721. doi: 10.1073/pnas.75.4.1718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kredich N. M., Martin D. V., Jr Role of S-adenosylhomocysteine in adenosinemediated toxicity in cultured mouse T lymphoma cells. Cell. 1977 Dec;12(4):931–938. doi: 10.1016/0092-8674(77)90157-x. [DOI] [PubMed] [Google Scholar]
  9. O'Dea R. F., Viveros O. H., Axelrod J., Aswanikaumar S., Schiffmann E., Corcoran B. A. Raipid stimulation of protein carboxymethylation in leukocytes by a chemotatic peptide. Nature. 1978 Mar 30;272(5652):462–464. doi: 10.1038/272462a0. [DOI] [PubMed] [Google Scholar]
  10. Pike M. C., Kredich N. M., Snyderman R. Requirement of S-adenosyl-L-methionine-mediated methylation for human monocyte chemotaxis. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3928–3932. doi: 10.1073/pnas.75.8.3928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Showell H. J., Freer R. J., Zigmond S. H., Schiffmann E., Aswanikumar S., Corcoran B., Becker E. L. The structure-activity relations of synthetic peptides as chemotactic factors and inducers of lysosomal secretion for neutrophils. J Exp Med. 1976 May 1;143(5):1154–1169. doi: 10.1084/jem.143.5.1154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Snyderman R., Altman L. C., Hausman M. S., Mergenhagen S. E. Human mononuclear leukocyte chemotaxis: a quantitative assay for humoral and cellular chemotactic factors. J Immunol. 1972 Mar;108(3):857–860. [PubMed] [Google Scholar]
  13. Snyderman R., Gewurz H., Mergenhagen S. E. Interactions of the complement system with endotoxic lipopolysaccharide. Generation of a factor chemotactic for polymorphonuclear leukocytes. J Exp Med. 1968 Aug 1;128(2):259–275. doi: 10.1084/jem.128.2.259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Snyderman R., Pike M. C., Fischer D. G., Koren H. S. Biologic and biochemical activities of continuous macrophage cell lines P388D1 and J774.1. J Immunol. 1977 Dec;119(6):2060–2066. [PubMed] [Google Scholar]
  15. Springer M. S., Goy M. F., Adler J. Sensory transduction in Escherichia coli: two complementary pathways of information processing that involve methylated proteins. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3312–3316. doi: 10.1073/pnas.74.8.3312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Springer W. R., Koshland D. E., Jr Identification of a protein methyltransferase as the cheR gene product in the bacterial sensing system. Proc Natl Acad Sci U S A. 1977 Feb;74(2):533–537. doi: 10.1073/pnas.74.2.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Stossel T. P. Contractile proteins in phagocytosis: an example of cell surface-to-cytoplasm communication. Fed Proc. 1977 Jul;36(8):2181–2184. [PubMed] [Google Scholar]
  18. Williams L. T., Snyderman R., Pike M. C., Lefkowitz R. J. Specific receptor sites for chemotactic peptides on human polymorphonuclear leukocytes. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1204–1208. doi: 10.1073/pnas.74.3.1204. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES