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Pentoxifylline inhibits actin polymerization in human neutrophils after stimulation by chemoattractant factor

Agents and Actions volume 31, pages 72–78 (1990)Cite this article

Abstract

Pentoxifylline (PTX) has been recently reported to stimulate PMN chemotaxis under dense agarose. The present study was designed to characterize the effect of PTX on action polymerization before and after stmulation by the chemotactic factor f-MLP- We used two different methods to determine the proportion of actin in the filamentous form: SDS-polyacrylamide gel electrophoresis to study the Triton X-100 insoluble cytoskeleton, and flow cytometry using fluorescent Rhodamine-Phalloidin to study actin conformation. PTX (10−3 M) did not affect the amount of F-actin (polymerized G-actin) incorporated into the cytoskeleton, but reduced total F-actin in a dose-dependent manner, at all concentrations of f-MLP used. Moreover, this inhibitory effect appeared more clearly in PMN with the higher activation ratios.

Thus F-actin is only partially incorporated into the cytoskeleton, and PTX-induced reduction of non-incorporated actin may reduce the stiffness of activated PMN. This could explain the increased chemotaxis of PMN across the small holes of dense agarose.

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References

  1. T. H. Howard and C. O. Oresajo,The kinetics of chemotactic peptide induced change in F-actin content, F-actin distribution and the shape of neutrophils. J. Cell Biol.101, 1078–1085 (1985).

    PubMed  Google Scholar 

  2. P. Sourbier, A. Perianin and J. Hakim,In vitro effect of pentoxifylline on human neutrophil function. InPentoxifylline and leukocyte function (Eds. G. L. Mandell and W. J. Novick), Haber Flora Inc. 1988.

  3. R. E. Duque and P. A. Ward,Quantitative assessment of neutrophil function by flow cytometry. Analytical and Quantitative Cytology and Histology,9, 42–48 (1987).

    PubMed  Google Scholar 

  4. W. A. Phillips, C. S. Hosking and M. J. Shelton,Removal of contaminating erythrocytes from human polymorphonuclear leukocyte preparations. Scand. J. Clin. Invest. 43, 621–627 (1983).

    PubMed  Google Scholar 

  5. R. D. Nelson, P. G. Quie and R. L. Simmons,Chemotaxis under agarose: a new and simple method for measuring chemotaxis and spontaneous migration of human polymorphonuclear leukocytes and monocytes. J. Immunol.115, 1650–1656 (1975).

    PubMed  Google Scholar 

  6. D. R. Philips, L. K. Jennings and H. H. Edwards,Identification of membrane proteins mediating the interaction of human platelets. J. Cell Biol.86, 77–86 (1980).

    PubMed  Google Scholar 

  7. U. K. Laemmli,Cleavage of structural proteins during the assembly of the head of bacteriophage T 4. Nature (Lond.)227, 680–685 (1970).

    Google Scholar 

  8. T. H. Howard and W. H. Meyer,Chemotactic peptide modulation of actin assembly and locomotion in neutrophils. J. Cell Biol.98, 1265–1271 (1984).

    PubMed  Google Scholar 

  9. M. P. Sheets, W. P. Wang and D. L. Kreutzer,Phosphoinositides as regulators of membrane skeletal activity. InWhite Cell Mechanics: basic science and clinical aspects (Eds. H. J. Meiselman, M. A. Lichtman and P. L. La Cells) pp. 87–94, Alan R. Liss, Inc., New York 1984.

    Google Scholar 

  10. G. S. Worthen, B. Schwab, E. L. Elson and G. P. Downey,Mechanics of stimulated neutrophils: cell stiffening induces retention in capillaries. Science,245, 183–186 (1989).

    PubMed  Google Scholar 

  11. G. W. Sullivan, T. N. Patselas, J. A. Redick and G. L. Mandell,Enhancement of chemotaxis and protection of mice from infection. Trans. Assoc. Am. Physicians,97, 337–345 (1984).

    PubMed  Google Scholar 

  12. T. Kuratsuji, S. Shimizu, K. Takaji, H. Hanabusa, M. Osana and T. Ichihashi,Effects of pentoxifylline on polymorphonuclear leukocyte function. Acta Paediatr. Jpn.27, 547–551 (1985).

    Google Scholar 

  13. D. E. Hammerschmidt, D. Kotasek, T. McCarthy, P. W. Huh, G. Freyburger and G. M. Vercellotti,Pentoxifylline inhibits granulocyte and platelet function, including granulocyte priming by platelet activating factor, J. Lab. Clin. Med.112, 254–263 (1988).

    PubMed  Google Scholar 

  14. E. A. Schmalzer and S. Chien,Filterability of subpopulations of leukocytes: effect of pentoxifylline. Blood64, 542–546 (1987).

    Google Scholar 

  15. A. Matrai and E. Ernst,Pentoxifylline improves white cell rheology in claudicants, Clin. Hemorheol.5, 483–491 (1985).

    Google Scholar 

  16. L. K. Jennings, J. E. B. Fox, H. H. Edwards and D. R. Phillips,Changes in the cytoskeletal structure of human platelets following thrombin activation. J. Biol. Chem.256, 6927–6932 (1981).

    PubMed  Google Scholar 

  17. M. K. Rao, J. Crawford, M. S. Currie and H. J. Cohen,Actin depolymerisation and inhibition of capping induced by pentoxifylline in human lymphocytes and neutrophils. J. Cell. Physiol.137, 577–582 (1988).

    PubMed  Google Scholar 

  18. G. W. Sullivan, H. T. Carper, W. J. Novick and G. L. Mandell,Inhibition of the inflammatory action of interleukin-1 and tumor necrosis factor (alpha) on neutrophil function by pentoxifylline. Infect. Immunol.56, 1722–1729 (1988).

    Google Scholar 

  19. H. Bessler, R. Gilgal, M. Djaldetti and I. Zahavi,Effect of pentoxifylline on the phagocytic activity, cAMP levels and superoxide anion production by monocytes and polymorphonuclear cells. J. Leuk. Biol.40, 747–754 (1986).

    Google Scholar 

  20. G. E. Chalkiadakis and A. Kostakis,Pentoxifylline in the treatment of experimental peritonitis in rats. Arch. Surg.120, 1141–1144 (1985).

    PubMed  Google Scholar 

  21. U. F. Schade and M. Schonhartig,Effect of pentoxifylline on the endotoxin-induced shock reaction. Clin. Hemorheol.6, 462 (1986).

    Google Scholar 

  22. P. K. W. Yu and J. A. Washington,Lack of antibacterial activity of pentoxifylline. Antimicrobial Agents and Chemotherapy30, 170–171 (1986).

    PubMed  Google Scholar 

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Affiliations

  1. Laboratoire d'Hémobiologie, Hôpital Cardiologique, Avenue Magellan, 33604, Pessac-Bordeaux, France

    G. Freyburger, F. Belloc & M. R. Boisseau

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  1. G. Freyburger
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  2. F. Belloc
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  3. M. R. Boisseau
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Freyburger, G., Belloc, F. & Boisseau, M.R. Pentoxifylline inhibits actin polymerization in human neutrophils after stimulation by chemoattractant factor. Agents and Actions 31, 72–78 (1990). https://doi.org/10.1007/BF02003224

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  • DOI: https://doi.org/10.1007/BF02003224

Keywords

  • Flow Cytometry
  • Activation Ratio
  • Small Hole
  • Human Neutrophil
  • Pentoxifylline