Diversity in Motile Responses of Human Neutrophil Granulocytes: Functional Meaning and Cytoskeletal Basis

  • Hansuli Keller
  • Verena Niggli
  • Arthur Zimmermann
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 297)


Neutrophil granulocytes are multifunctional cells, capable of locomotion, Chemotaxis, adhesion, pinocytosis, phagocytosis, intracellular killing or degradation and exocytosis. Several of the functions require generation of force and may thus be associated with different forms of motility. In the circulating blood of healthy individuals neutrophils are in a relatively quiescent state, i.e. they are spherical and nonmotile. Activation and regulation of neutrophil functions can, to some extent, occur in a selective manner. Most agonists activate only some neutrophil functions but not others. Or they stimulate at least some functions to a much greater extent than others. Chemotaxis for example is an important neutrophil function, but only few agonists are actually chemotactic, while many others are not. Furthermore an agonist, e.g. a chemotactic factor, may elicit pinocytosis or Chemotaxis at lower concentrations than exocytosis (Davis et al., 1986). Such qualitative, quantitative and temporal differences may help to understand the relationship, if any, between these functions. Thus, the F-actin peak preceeds the time maximum for pinocytosis (Davis et al., 1986), and the maximal pinocytotic response occurs at an earlier time point than full development of polarity (Fig. 1) and locomotion.


Shape Change Human Neutrophil Phorbol Ester Chemotactic Factor Surface Projection 
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  1. Anderson, D. C., Wible, L. J., Hughes, B. J., Smith, C. W., Brinkley, B. R.: Cytoplasmic microtubules in polymorphonuclear leukocytes: Effects of chemotactic stimulation and colchicine. Cell 31:719 (1982).PubMedCrossRefGoogle Scholar
  2. Boxer, L. A., Yoder, M., Bonsib, S., Schmidt, M., Ho, P., Jersild, R., Baehner, R. L.: Effects of a chemotactic factor, N-formyl-methionyl peptide, on adherence, superoxide anion generation, phagocytosis, and microtubule assembly of human polymorphonuclear leukocytes. J. Lab. Clin. Med. 83:506 (1979).Google Scholar
  3. Cox, C. C., Dougherty, R. W., Ganong, B. R., Bell, R. M., Niedel, J. E., Snyderman, R.: Differential stimulation of the respiratory burst and lysosomal enzyme secretion in human polymorphonuclear leukocytes by synthetic diacylglycerols. J. Immunol. 136:4611 (1986).PubMedGoogle Scholar
  4. Daukas, G., Lauffenburger, D. A., Zigmond, S.: Reversible pinocytosis in polymorphonuclear leukocytes. J. Cell Biol. 96:1642 (1983).PubMedCrossRefGoogle Scholar
  5. Davis, B. H., Walter, R. J., Pearson, C. B., Becker, E. L., Oliver, J. M.: Membrane activity and topography of f-Met-Leu-Phe-treated polymorphonuclear leukocytes. Acute and sustained responses to chemotactic peptide. Am. J. Pathol. 108:206 (1982).PubMedGoogle Scholar
  6. Davis, B. H., McCabe, E., Langweiler, M.: Characterization of f-Met-Leu-Phe-stimulated fluid pinocytosis in human polymorphonuclear leukocytes by flow cytometry. Cytometry 7:251 (1986).PubMedCrossRefGoogle Scholar
  7. Devreotes, P. N., Zigmond, S.H.: Chemotaxis in eukaryotic cells: a focus on leucocytes and dictyostelium. Ann. Rev. Cell Biol. 4: 649 (1988).PubMedCrossRefGoogle Scholar
  8. Euteneuer, U., Schliwa, M.: Evidence for an involvement of actin in the positioning and motility of centrosomes. J. Cell Biol. 101: 96 (1985).PubMedCrossRefGoogle Scholar
  9. Evans, J. F., Leblanc, Y., Fitzsimmons, B. J., Charleson, S., Nathaniel, D., Léveillé, C.: Activation of leukocyte movement and displacement of [3H]leukotriene B4 from leukocyte membrane preparations by (12R)-and 12S)-hydroxyeicosatetraenoic acid. Biochim. Biophys. Acta 917:406 (1987).PubMedCrossRefGoogle Scholar
  10. Fechtheimer, M., Zigmond, S. H.: Changes in cytoskeletal proteins of polymorphonuclear leucocytes induced by chemotactic peptides. Cell Motil. 3:349 (1983).CrossRefGoogle Scholar
  11. Fletcher, M. P., Seligmann, B. E., Gallin, J. I.: Correlation of human neutrophil secretion, chemoattractant receptor mobilization, and enhanced functional capacity. J. Immun. 128:941 (1982).PubMedGoogle Scholar
  12. Ford-Hutchinson, A. W., Bray, M. A., Doig, M. V., Shipley. M. E., Smith, M. J.H.: Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature 286:264 (1980).PubMedCrossRefGoogle Scholar
  13. Gallin, J. I., Wright, D. G., Schiffman, E.: Role of secretory events in modulating human neutrophil Chemotaxis. J. Clin. Invest. 62:1364 (1978).PubMedCrossRefGoogle Scholar
  14. Hafstrom, I., Palmblad, J., Malmsten, C. L., Radmark, O., Samuelsson, B.: Leukotriene B4 — A stereospecific stimulator for release of lysosomal enzymes from neutrophils. FEBS Lett. 130:146 (1981).PubMedCrossRefGoogle Scholar
  15. Haston, W. S., Shields, J.M.: Neutrophil leucocyte Chemotaxis: a simplified assay for measuring polarising responses to chemotactic factors. J. Immunol. Methods 81:229 (1985).PubMedCrossRefGoogle Scholar
  16. Hoult, J. R. S., Nourshargh, S.: Phorbol myristate acetate enhances human polymorphonuclear neutrophil release of granular enzymes but inhibits chemokinesis. Br. J. Pharmac. 86:533 (1985).CrossRefGoogle Scholar
  17. Howard, T. H., Oresajo, C. O.: A method for quantifying F-actin in chemotactic peptide activated neutrophils: study of the effect of tBOC peptide. Cell Motil. 5:545 (1985).PubMedCrossRefGoogle Scholar
  18. Jesaitis, A. J., Bokoch, G. M., Tolley, J.O., Allen, R.A.: Lateral segregation of neutrophil chemotactic receptors into actin- and fodrin-rich plasma membrane microdomains depleted in guanyl nucleotide regulatory proteins. J. Cell Biol. 107:921 (1988).PubMedCrossRefGoogle Scholar
  19. Keller, H. U., Bessis, M.: Migration and Chemotaxis of anucleate cytoplasmic leukocyte fragments. Nature 2 58:723 (1975).CrossRefGoogle Scholar
  20. Keller, H. U., Wilkinson, P. C., Abercrombie, M., Beckers, E. L., Hirsch, J. G., Miller, M. E., Ramsey, W. S., Zigmond, S. H.: A proposal for the definition of terms related to locomotion of leucocytes and other cells. Clin. exp. Immunol. 27:377 (1977).PubMedGoogle Scholar
  21. Keller, H.U.: Motility, cell shape, and locomotion of neutrophil granulocytes. Cell Motility 3:47 (1983).PubMedCrossRefGoogle Scholar
  22. Keller, H. U., Zimmermann, A., Cottier, H.: Crawling-like movements, adhesion to solid substrata and chemokinesis of neutrophil granulocytes. J. Cell Sci. 64:8 (1983).Google Scholar
  23. Keller, H.U., Naef, A., Zimmermann, A.: Effects of colchicine, vinblastine and nocodazole on polarity, motility, Chemotaxis and cAMP levels of human polymorphonuclear leukocytes. Exp. Cell. Res. 153:173 (1984).PubMedCrossRefGoogle Scholar
  24. Keller, H. U., Zimmermann, A.: Shape, movement and function of neutrophil granulocytes. Biomed. & Pharmacother. 41:285 (1987).Google Scholar
  25. Keller, H.U., Niggli, V., Zimmermann, A.: Diacylglycerols and PMA induce actin polymerization and distinct shape chang es in lymphocytes: relation to fluid pinocytosis and locomotion. J. Cell Sci. 93:457 (1989).PubMedGoogle Scholar
  26. Keller, H. U., Niggli, V., Zimmermann, A., Portmann R.: The protein kinase C inhibitor H-7 activates human neutrophils: effect on shape, actin polymerization, fluid pinocytosis and locomotion. Subm. (1989).Google Scholar
  27. Lehmeyer, J. E., Snyderman, R., Johnston, R. B.: Stimulation of neutrophil oxidative metabolism by chemotactic peptides: Influence of calcium ionconcentration and cytochalasin B and comparison with stimulation by phorbol myristate acetate. Blood 54:35 (1979).PubMedGoogle Scholar
  28. Lewis, W.H.: On the locomotion of the polymorphonuclear neutrophils of the rat in autoplasma cultures. Bull. Johns Hopkins Hosp. 55:273 (1934).Google Scholar
  29. Malawista, S. E.: Microtubule function in human blood polymorphonuclear leukocytes: analysis through heat-induced lesions. In: Dynamic Aspects of Microtubule Biology (Soifer D, ed), Ann. NY Acad. Sci., Vol. 466, pp. 859 (1986).Google Scholar
  30. Niggli, V., Jenni, V.: Actin-associated proteins in human neutrophils: identification and reorganization upon cell activation. Eur. J. Cell Biol. 49:366 (1989).PubMedGoogle Scholar
  31. Nourshargh, S., Hoult, J. R. S.: Divergent effects of co-carcinogenic phorbol esters and a synthetic diacylglycerol on human neutrophil chemokinesis and granular enzyme secretion. Br. J. Pharmac. 91:557 (1987).CrossRefGoogle Scholar
  32. Omann, G. M., Allen, R. A., Bokoch, G. M., Painter, R. G., Traynor, A. E., Sklar, L.: Signal transduction and cytoskele-tal activation in the neutrophil. Physiol. Rev. 67:285 (1987).PubMedGoogle Scholar
  33. Parysek, C. M., Eckert, B. S.: Vimentin filaments in spreading, randomly locomoting and f-met-leu-phe-treated neutrophils. Cell Tissue Res. 235:575 (1984).PubMedCrossRefGoogle Scholar
  34. Rao, K. M., Varani, J.: Actin polymerization induced by chemotactic peptide and concanavalin A in rat neutrophils. J. Immunol. 129:1605 (1982).PubMedGoogle Scholar
  35. Robinson, J. M., Badwey, J. A., Karnovsky, M. L., Karnovsky, M. J.: Cell surface dynamics of neutrophils stimulated with phorbol esters or retinoids. J. Cell Biol. 105:417 (1987).PubMedCrossRefGoogle Scholar
  36. Rollins, T. E., Zanolari, B., Springer, M. S., Guindon, Y., Zamboni, R., Lau, C.-K., Rokach, J.: Synthetic leukotriene B4 is a potent chemotaxin but a weak secretagogue for human PMN. Prostaglandins 25:281 (1983).PubMedGoogle Scholar
  37. Roos, F. J., Zimmermann, A., Keller, H. U.: Effect of phorbol myristate acetate and the chemotactic peptide fNLPNTL on shape and movement of human neutrophils. J. Cell Sci. 88:399 (1987).PubMedGoogle Scholar
  38. Schliwa, M., Pryzwanski, K. B., Euteneuer, U.: Centrosome splitting in neutrophils: an unusual phenomenon related to cell activation and motility. Cell 31:705 (1982).PubMedCrossRefGoogle Scholar
  39. Schliwa, M., Pryzwanski, K. B., Borisy, G. G.: Tumor promoter-induced centrosome splitting in human polymorphonuclear leukocytes. Eur. J. Cell Biol. 32:75–85 (1983).PubMedGoogle Scholar
  40. Sha’afi, R. I., White, J. R., Molski, T. F. P., Shefzyk, J., Volpi, M., Naccache, P. H., Feinstein, M. B.: Phorbol 12-myri-state 13-acetate activates rabbit neutrophils without an apparent rise in the level of intracellular free calcium. Biochem. Biophvs. Res. Commun. 114:638 (1983).CrossRefGoogle Scholar
  41. Sha’afi, R. I., Molski, T. F. P.: Signalling for increased cytoskeletal actin in neutrophils. Biochem. Biophys. Res. Commun. 145:934 (1987).PubMedCrossRefGoogle Scholar
  42. Sheterline, P., Rickard, J. E., Boothroyd, B., Richards, R. C.: Phorbol ester induces rapid actin assembly in neutrophil leucocytes independently of changes in [Ca2+] and pHi. J. Muscle Res. Cell Motil. 7:405 (1986).PubMedCrossRefGoogle Scholar
  43. 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 enzyme secretion for neutrophils. J. Exp. Med. 143:1154 (1976).PubMedCrossRefGoogle Scholar
  44. Spiegel, J. E., Schultz Beardsley, D., Southwick, F. S., Cux, S. E.: An analogue of the erythroid membrane skeletal protein 4.1 in non-erythroid cells. J. Cell Biol. 99:886 (1984).PubMedCrossRefGoogle Scholar
  45. Valerius, N. H., Stendahl, O., Hartwig, J. H., Stossel, T. P.: Distribution of actin-binding protein and myosin in polymorphonuclear leucocytes during locomotion and phagocytosis. Cell 24:195 (1981).PubMedCrossRefGoogle Scholar
  46. White, J. G., Estensen, R.D.: Selective labilization of specific granules in polymorphonuclear leukocytes by phorbol myristate acetate. Am. J. Pathol. 75:45 (1974).PubMedGoogle Scholar
  47. White, J. R., Naccache, P. H., Sha’afi, R. I.: The synthetic chemotactic peptide formyl-methionyl-leucyl-phenyl-alanine causes an increase in actin associated with the cytoskeleton in neutrophils. Biochem. Biophys. Res. Commun. 108:1144 (1982).PubMedCrossRefGoogle Scholar
  48. White, J. R., Huang, C.-K., Hill, J. Jr., Naccache, P. H., Becker, E. L., Sha’afi, R. I.: Effect of phorbol 12-myristate 13-acetate and its analogue 4a-phorbol 12,13-didecanoate on protein phosphorylation and lysosomal enzyme release in rabbit neutrophils. J. Biol. Chem. 259:8605 (1984).PubMedGoogle Scholar
  49. Wright, T. M., Hoffman, R. D., Nishijima, J., Jakoi, L., Snyderman, R., Shin H. S.: Leukocyte chemoattraction by 1,2-diacylglycerol. Proc. Natl. Acad. Sci. 85:1869 (1988).PubMedCrossRefGoogle Scholar
  50. Zigmond, S. H., Sullivan, S. J.: Sensory adaptation of leukocytes to chemotactic peptides. J. Cell. Biol. 82:517 (1979).PubMedCrossRefGoogle Scholar
  51. Zigmond, S. H., Levitsky, H. I., Kreel, B. J.: Cell polarity: an examination of its behavioral expression and its consequences for polymorphonuclear leukocyte Chemotaxis. J. Cell Biol. 89:585 (1981).PubMedCrossRefGoogle Scholar
  52. Zimmermann, A., Keller, H. U., Cottier, H.: Heavy water (D20)-induced shape changes, movements and F-actin redistribution in human neutrophil granulocytes. Eur. J. Cell Biol. 47:320 (1988).PubMedGoogle Scholar
  53. Zimmermann, A., Gehr, P., Keller, H. U.: Diacylglycerol-in-duced shape changes, movements and altered F-actin distribution in human neutrophils. J. Cell Sci. 90:657 (1988).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Hansuli Keller
    • 1
  • Verena Niggli
    • 1
  • Arthur Zimmermann
    • 1
  1. 1.Institute of PathologyUniversity of BernBernSwitzerland

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