Summary
Incubation of human polymorphonuclear leukocytes (PMNL) or thioglycollate-stimulated mouse peritoneal macrophages with the phagocytosis-stimulating peptide, tuftsin (2.5 × 10−7 M, at 37 °C), caused an increase of 89–90% in intracellular cGMP levels, accompanied by a decrease of 20–25% in intracellular cAMP levels. Significant changes in cyclic nucleotide levels were detectable after 4 min of incubation, were maximal at 10–20 min and persisted for at least 60 min. The concentration dependences of the stimulatory effect of tuftsin on modulation of intracellular levels of cyclic nucleotides and on phagocytosis are similar, suggesting a cause and effect relationship between the two phenomena. This notion is further supported by the finding that 8-Br-cGMP and 8-Br-cAMP elicit stimulatory and inhibitory effects on macrophage phagocytosis, respectively. Measurement of 45Ca2+ influx into PMNL and macrophages in the presence and absence of tuftsin did not reveal any change in 45Ca2+ uptake from the media. However, tuftsin did enhance release of 45Ca2+ from cells preloaded with the isotope. Results suggest that modulation of both the amount of cell-associated 45Ca2+ and the intracellular levels of cyclic nucleotides are key steps in the mechanism by which tuftsin augments phagocytosis.
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References
Najjar, V. A. and Nishioka, K., 1970. Nature 228, 672–673.
Constantopoulos, A. and Najjar, V. A., 1972. Cytobios. 6, 97–100
Martinez, J., Winternitz, F. and Vindel, J., 1977. Eur. J. Med. Chem. Chim. Therap. 12, 511–516.
Nishioka, K., Satoh, P. S., Constantopoulos, A. and Najjar, V. A., 1973. Biochim. Biophys. Acta 310, 230–237.
Tzehoval, E., Segal, S., Stabinsky, Y., Fridkin, M., Spirer, Z. and Feldman, M., 1978. Proc. Nall. Acad. Sci. USA 75, 3400–3404.
Fridkin, M., Stabinsky, Y., Zakuth, V. and Spirer, Z., 1977. Biochim. Biophys. Acta 496, 203–211.
Stabinsky, Y., Fridkin, M., Zakuth, V. and Spirer, Z., 1978. Int. J. Peptide Protein Res. 12, 130–135.
Stabinsky, Y., Pundak, S., Wilchek, M. and Fridkin, M., 1978. IUPAC Second International Symposium on Organic Chemistry, Jerusalem, Haifa, Israel, Abst. p. 69.
Stabinsky, Y., Gottlieb, P., Zakuth, V., Spirer, Z. and Fridkin, M., 1978. Biochem. Biophys. Res. Commun. 83, 599–606.
Bar-Shavit, Z., Stabinsky, Y., Fridkin, M. and Goldman, R., 1979. J. Cell Physiol. 100, 55–62.
Cox, J. D. and Karnovsky, M. D., 1973. J. Cell Biol. 59, 480–490.
Ignarro, L. J. and Cech, S. Y., 1976. Proc. Soc. Exp. Biol. Mod. 151, 448–452.
Boyum, A., 1978. Scand. J. Clin. Lab. Invest. 21, Suppl. 97, 77–89.
Williams, L. T., Synderman, R., Pike, M. C. and Lefkowitz, R. J., 1977. Proc. Natl. Acad. Sci. USA 74, 1204–1208.
Rivkin, I., Rosenblatt, J. and Becker, E. L., 1975. J. Immunol. 115, 1126–1134.
Hill, H. R., 1978. In Leukocytes Chemotaxis: Methods, Physiology and Clinical Implications, Edited by J. I. Gallin and P. G. Quie, Raven Press, New York, pp. 179–193.
Spirer, Z., Zakuth, V., Golander, A. and Bogair, N., 1975. Experientia 31, 118–119.
Zurier, R. B., Weissmann, G., Hoffstein, S., Kammerman, S. and Tai, H. H., 1974. J. Clin. Invest. 53, 297–309.
Ignarro, L. J. and George, W. J., 1974. Proc. Natl. Acad. Sci. USA 71, 2027–2031.
Estensen, R. D., Hill, H. R., Quie, P. G., Hogan, N. and Goldberg, N. A., 1973. Nature 245, 458–460.
Sandler, J. A., Gallin, J. I. and Vaughan, M., 1975. J. Cell. Biol. 67, 480–484.
Hill, H. R., Estensen, R. D., Quie, P. G., Hogan, N. A. and Goldberg, N. D., 1975. Metabolism 24, 447–456.
Bourne, H. R., Lehrer, R. I., Cline, M. J. and Melmon, K. L., 1971. J. Clin. Inves. 50, 920–929.
Ignarro, L. J. and Cech, S. Y., 1975. J. Cyclic Nucleotide Res. 1, 283–292.
Goldberg, N. D. and Haddox, M. K., 1977. Ann. Rev. Biochem. 46, 823–896.
Schultz, G., Hardman, J. G., Schultz, K., Baird, C. E. and Sutherland, E. W., 1973. Proc. Natl. Acad. Sci. USA 70, 3889–3893.
Smith, R. J. and Ignarro, L. J., 1975. Proc. Natl. Acad. Sci. USA 72, 108–112.
Ferrendelli, J. A., Kinscherf, D. A. and Chang, M. M., 1973. Mol. Pharmacol. 9, 445–454.
May, R. J., Conlon, T. P., Erspamer, V. and Gardner, J. D., 1978. Am. J. Physiol. 235, E112-E118.
Manganiello, V. and Vaughan, M., 1972. Proc. Natl. Acad. Sci. USA 69, 269–273.
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Stabinsky, Y., Bar-Shavit, Z., Fridkin, M. et al. On the mechanism of action of the phagocytosis-stimulating peptide tuftsin. Mol Cell Biochem 30, 71–77 (1980). https://doi.org/10.1007/BF00227920
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DOI: https://doi.org/10.1007/BF00227920