Advertisement

Novel Neutrophil Agonists: Oxidatively-Fragmented Phosphatidylcholines

  • Patricia L. Smiley
  • Kamala D. Patel
  • Kay E. Stremler
  • Guy A. Zimmerman
  • Stephen M. Prescott
  • Thomas M. McIntyre
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

Platelet-activating factor (PAF) is a phospholipid autocoid that plays a role in both physiologic and pathologic events. Its diverse biologic activities include activation of platelets, neutrophils, macrophages, and other cell types not directly involved in the inflammatory process1. When exogenously administered, PAF produces the symptoms of anaphylactic shock. It is obviously important that the synthetic and degradative enzymes controlling its production and metabolism be tightly regulated. PAF acts via receptors2 present on the cell membrane of target cells; the structural requirements for high affinity binding and activation of PAF receptors have been well characterized3. The ether linkage at the sn-1 position, short chain acetyl residue at the sn-2 position, and phosphocholine group at the sn-3 position of PAF all play an important role in this high affinity recognition. Phospholipids other than PAF are capable of binding to and activating the PAF receptor. For example the 1-O-alkyl-2-propionoyl homolog is twice as potent as PAF. Other homologs are active but less potent. The sn-2 butyroyl homolog is 30-100-fold less potent than PAF3, while the succinoyl and glutaroyl homologs are several hundred-fold less potent3. The presence of an ester linkage at the sn-1 position instead of an ether linkage results in a several hundred-fold loss in potency3.

Keywords

Rhizopus Arrhizus Butyl Hydroperoxide Oxidative Fragmentation Bond Rearrangement Phosphocholine Group 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Hanahan, D. J. (1986) Annu. Rev. Biochem. 55, 483–509PubMedCrossRefGoogle Scholar
  2. 2.
    Honda, Z., Nakamura, M., Mild, I., Minami, M., Watanabe, T., Seyama, Y., Okado, H., Toh, H., Ito, K., Miyamoto, T., and Shimizu, T. (1991) Nature 349, 342–346PubMedCrossRefGoogle Scholar
  3. 3.
    Blank, M. L., Cress, E. A., Lee, T. C., Malone, B., Suries, J. R., Piantodosi, C., Hajdu, J., and Snyder, F. (1982) Res. Commun. Chem. Pathol. Pharmacol. 39, 291–309Google Scholar
  4. 4.
    Yoshida, J. L, Tokumura, A., Fukuzawa, K., Terao, M., Takauchi, K., and Tsukatani, H. (1986) J. Pharm. Pharmacol. 38, 878–882PubMedCrossRefGoogle Scholar
  5. 5.
    Tokumura, A., Kamiyasu, K., Takauchi, K., and Tsukatani, H. (1987) Biochem. Biophys. Res. Commun. 145, 415–425PubMedCrossRefGoogle Scholar
  6. 6.
    Tokumura, A., Asai, T., Takauchi, K., Kamiyasu, K., Ogawa, T., and Tsukatani, H. (1988) Biochem. Biophys. Res. Commun. 155, 863–869PubMedCrossRefGoogle Scholar
  7. 7.
    Tokumura, A., Takauchi, K., Mai, T., Kamiyasu, K., Ogawa, T., and Tsukatani, H. (1989) J. Lipid Res. 30, 219–224PubMedGoogle Scholar
  8. 8.
    Rabe, H., Kushi, Y., Handa, S., and Inoue, K. (1988) Biochem. Biophys. Acta 962, 8–15CrossRefGoogle Scholar
  9. 9.
    McCord, J. M. (1985) N. Engl. J. Med. 312, 159–163PubMedCrossRefGoogle Scholar
  10. 10.
    Engler, R. L. (1989) Am. J. Cardiol. 63, 19E - 23EPubMedCrossRefGoogle Scholar
  11. 11.
    Smiley, P. L., Stremler, K. E., Prescott, S. M., Zimmerman, G. A., and McIntyre, T. M. (1991) J. Biol. Chem. 266, in pressGoogle Scholar
  12. 12.
    Zimmerman, G. A., and McIntyre, T. M. (1988) J. Clin. Invest. 81, 531–537PubMedCrossRefGoogle Scholar
  13. 13.
    Stremler, K. E., Stafforini, D. M., Prescott, S. M., and McIntyre, T. M. (1991) J. Biol. Chem. 266, in pressGoogle Scholar
  14. 14.
    Bligh, E. G., and Dyer, W. J. (1959) Can. J. Biochem. Physiol. 37, 911–917PubMedCrossRefGoogle Scholar
  15. 15.
    Frenkel, E. N. (1982) Prog. Lipid Res. 22, 1–33CrossRefGoogle Scholar
  16. 16.
    Frenkel, E. N., Neff, W. E., and Rohwedder, W. K. (1977) Lipids 12, 901–907CrossRefGoogle Scholar
  17. 17.
    Toth, K. M., Harlan, J. M., Beehler, C. J., Berger, E. M., Parker, N. B., Linas, S. L., and Repine, J. E. (1989) Free Radical Biol. & Med. 6, 457–466CrossRefGoogle Scholar
  18. 18.
    Lewis, M. S., Whatley, R. E., Cain, P., McIntyre, T. M., Prescott, S. M., and Zimmerman, G. A. (1988) J. Clin. Invest. 82, 2045–2055PubMedCrossRefGoogle Scholar
  19. 19.
    Patel, K. D., Zimmerman, G. A., Prescott, S. M., McEver, R. P., and McIntyre, T. M. (1991) J. Cell Biol. 112, 749–759PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Patricia L. Smiley
    • 3
  • Kamala D. Patel
    • 4
  • Kay E. Stremler
    • 1
  • Guy A. Zimmerman
    • 1
  • Stephen M. Prescott
    • 2
    • 4
  • Thomas M. McIntyre
    • 2
    • 4
  1. 1.Nora Eccles Harrison Cardiovascular ResearchUniversity of UtahSalt Lake CityUSA
  2. 2.Departments of Internal MedicineUniversity of UtahSalt Lake CityUSA
  3. 3.Departments of PharmacologyUniversity of UtahSalt Lake CityUSA
  4. 4.Departments of BiochemistryUniversity of UtahSalt Lake CityUSA

Personalised recommendations