Attenuation of spontaneous pseudopod formation in human neutrophils by pentoxifylline
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Abstract
The effects of pentoxifylline (PTX) on spontaneous pseudopod formation in neutrophils in response to the tripeptide formyl-Met-Leu-Phe (fMLP), endotoxin, human complement C5a, and leukotriene B4 (LTB4) were examined in autologous plasma. Unseparated supernatant leukocyte suspensions from fresh heparinized venous human blood were incubated with PTX (0-5 mM) for 25 min and then stimulated for 5–25 min within a range of concentrations of fMLP, endotoxin, complement C5a, and LTB4. The cell suspensions were fixed with glutaraldehyde and stained with crystal violet in acetic acid; the percentage of neutrophils with pseudopods was determined under high-resolution light microscope. The results show that PTX significantly decreases formation of pseudopods in the presence of all four stimulators. The mechanism of pseudopod suppression appears to be independent of the adenosine receptor. PTX and its analogues, HWA 138 and HWA 448, decreased pseudopod formation by similar amounts when stimulated with 10−8M fMLP. These results suggest that PTX may improve microvascular perfusion and attenuate neutrophilmediated injury by reducing the degree of neutrophil pseudopod formation in free suspension and microvascular entrapment.
Index Entries
Neutrophil activation actin polymerization formyl-Met-Leu-Phe leukotriene endotoxin complementPreview
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References
- 1.Schmid-Schönbein, G. W. and Engler, R. L. (1986),Am. J. Cardiovasc. Path. 1, 15–30.Google Scholar
- 2.Hernandez, L. A., Grisham, M. B., Twohig, B., Arfors, K. E., Harlan, J. M., and Granger, D. N. (1987),Am. J. Physiol. 253, H699-H703.PubMedGoogle Scholar
- 3.Hogg, J. C. (1987),Physiol. Rev. 67, 1249–1295.PubMedGoogle Scholar
- 4.Gerrity, R. G. (1981),Am. J. Path. 103, 181–190.PubMedGoogle Scholar
- 5.Weiss, S. J. (1989),N. Eng. J. Med. 320, 365–376.CrossRefGoogle Scholar
- 6.Schröder, S., Palinski, W., and Schmid-Schönbein, G. W. (1991),Am. J. Pathol. 139, 81–100.PubMedGoogle Scholar
- 7.Barroso-Aranda, J., Schmid-Schönbein, G. W., Zweifach, B. W., and Engler, R. L. (1988),Circ. Res. 63, 437–447.PubMedGoogle Scholar
- 8.Entman, M. L., Michael, L., Rossen, R. D., Dreyer, W. J., Anderson, D. C., Taylor, A. A., and Smith, C. W. (1991),FASEB J 5, 2529–2537.PubMedGoogle Scholar
- 9.del Zoppo, G. J., Schmid-Schönbein, G. W., Mori, E., Copeland, B. R., and Chang, C.-M. (1991),Stroke 22, 1276–1283.PubMedGoogle Scholar
- 10.Barroso-Aranda, J. and Schmid-Schönbein, G. W. (1989),Am. J. Physiol. 257, H846-H852.PubMedGoogle Scholar
- 11.Hakim, J., Mandell, G. L., and Novick, W. J. J., eds., (1990),Pentoxifylline and Analogues: Effect on Leukocyte Function, S. Karger, Basel, pp. 1–8, 38–47, 64–70, 97–103.Google Scholar
- 12.Sullivan, G. W., Carper, H. T., Novick, W. J. J., and Mandell, G. L. (1988),Infect. Immun. 56, 1722–1729.PubMedGoogle Scholar
- 13.Barroso-Aranda, J. and Schmid-Schönbein, G. W. (1990),Biorheology 27, 401–418.PubMedGoogle Scholar
- 14.Schmid-Schönbein, G. W., Skalak, R., Sung, K.-L.-P., and Chien, S. (1982)White Blood Cells, Morphology and Rheology as Related to Function, Born, G. V. R., Bagge, U., and Gaehtgens, P., edds., Martinus Nijhoff, The Hague, pp. 21–31.Google Scholar
- 15.Salmon, J. E. and Cronstein, B. N. (1990),J. Immun. 145, 2235–2240.PubMedGoogle Scholar
- 16.Currie, M. S., Rao, K. M. K., Padmanabhan, J., Jones, A., Crawford, J., and Cohen, H. J. (1990),J. Leuko Biol. 47, 244–250.PubMedGoogle Scholar
- 17.Mandell, G. L. and Novick, W. J. J. eds., (1988),Pentoxifylline and Leukocyte Function, Hoechst-Roussel Pharmaceuticals, Sommerville, NJ, pp. 37–48, 56–67, 82–95, 105–114.Google Scholar
- 18.Chien, S., Schmalzer, E. A., Lee, M. M. L., Impelluso, T., and Skalak, R. (1983),Biorheology 20, 11–22.PubMedGoogle Scholar
- 19.Schmalzer, E. A., and Chien, S. (1984),Blood 64, 542–546.PubMedGoogle Scholar
- 20.Endres, S., Sinha, B., Stoll, D., Fülle, H.-J., and Schönharting, M. M. (1991),Circ. Shock 34, 142 (Abstract).Google Scholar
- 21.Bessler, H., Gilgal, R., Djaldetti, M., and Zahavi, I. (1986),J. Leuko. Biol. 40, 747–754.PubMedGoogle Scholar
- 22.Mills, J. M. and Lubin, M. (1986),Am. J. Physiol. 250, C319-C324.PubMedGoogle Scholar
- 23.Rao, K. M. K., Crawford, J., Currie, M. S., and Cohen, H. J. (1988),J. Cell. Physiol 137, 577–582.PubMedCrossRefGoogle Scholar
- 24.Strieker, R. M., Remick, D. G., Ward, P. A., Spengler, R. N., Lynch, J. P. I., Larrick, J., and Kunkel, S. L. (1988),Biochem. Biophys. Res. Comm. 155, 1230–1236.CrossRefGoogle Scholar