Lipid Model Membrane Studies on Immune Cytotoxic Mechanisms

  • Robert Blumenthal
  • John N. Weinstein
  • Pierre Henkart
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 84)


The immune lysis of cells is thought to involve an initial breakdown of the membrane permeability barrier to small ions, with eventual colloid osmotic swelling and disruption of the cell. Lipid model membranes have been used by several workers to study complement-mediated cytotoxicity. We have introduced a system based on the planar lipid bilayer in which mechanisms of lymphocyte-mediated cytotoxicity can be investigated. We have shown that human lymphocytes induce membrane conductance increases (i.e., ion permeability increases) of several orders of magnitude in bilayers containing a hapten (dinitrophenyl) if specific antibody (IgG anti-trinitrophenyl) is added. The conductance increase occurs only when the membrane voltage is positive on the lymphocyte side, as would be the case with a target cell membrane. A variety of controls (in which one or another component of the system is altered or omitted) are all negative, indicating that this effect has essentially the same immunospecificity as lymphocyte-mediated killing of antibody-coated target cells. The results suggest that killer lymphocytes can act on membranes directly to cause permeability increases without participation of other target cell components. Moreover, target cell membrane protein appears unnecessary for the effect. Measurements of membrane potential in the presence of salt concentration differences suggest that the conductance-inducing material has a mild (3:1) selectivity for anions over cations.


Conductance Increase Conductance Change Phosphatidyl Ethanolamine Planar Lipid Bilayer Target Cell Membrane 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Müller-Eberhard, H.J.: Harvey Lectures 66 (1972) 75.Google Scholar
  2. 2.
    Cerottini, J.C. and Brunner, K.T.: Adv. Immunol. 18 (1974) 67.PubMedCrossRefGoogle Scholar
  3. 3.
    Robinson, J.R.: Pathobiology of Cell Membranes, Vol. I, Ch. 4, (Trump, B.F. and Arstila, A.U. eds.) Academic, New York (1975).Google Scholar
  4. 4.
    Seeman, P.: Fed. Proc. 33 (1974) 2116.PubMedGoogle Scholar
  5. 5.
    Kedem, O. and Katchalsky, A.: Biochim. Biophys. Acta 27 (1958) 229.PubMedCrossRefGoogle Scholar
  6. 6.
    Staverman, A.S.: Rec. Trav. Chim. 70 (1951) 344.CrossRefGoogle Scholar
  7. 7.
    Diamond, J. and Wright, E.M.: Annu. Rev. Physiol. 31 (1969) 581PubMedCrossRefGoogle Scholar
  8. 8.
    Bangham, A.D., Hill, M.W. and Miller, N.G.A.: Methods in Membrane Biology, Vol. I, Ch. 1, (Korn, E.D., ed.) Plenum, New York (1974).Google Scholar
  9. 9.
    Mueller, P., Rudin, D.O., Tien, H.T. and Westcott, W.C.: 1 (1964) 379.Google Scholar
  10. 10.
    Bean, R.C., Shepherd, W.C., Chan, H. and Eichner, J.: J. Gen. Physiol. 53 (1969) 741.PubMedCrossRefGoogle Scholar
  11. 11.
    Kinsky, S.C.: Biochim. Biophys. Acta. 265 (1972) 1.PubMedGoogle Scholar
  12. 12.
    Del Castillo, J., Rodriquez, A., Romero, C.A., and Sanchez, V.: Science 153 (1966) 185.PubMedCrossRefGoogle Scholar
  13. 13.
    Barfort, P., Arquilla, E.R. and Vogelhut, P.O.: Science 160 (1968) 119.CrossRefGoogle Scholar
  14. 14.
    Wobschall, E. and McKeon, C.: Biochim. Biophys. Acta. 413 (1975) 317.PubMedCrossRefGoogle Scholar
  15. 15.
    Blumenthal, R. and Shamoo, A.E.: Ann. N.Y. Acad. Sci. 264 (1975) 483.PubMedCrossRefGoogle Scholar
  16. 16.
    Michaels, D.W., Abramovitz, A.S., Hammer, C.H., and Mayer, M.M.: Proc. Nat. Acad. Sci. USA (1976) In press.Google Scholar
  17. 17.
    Henkart, P. and Blumenthal, R.: Proc. Nat. Acad. Sci. USA 72 (1975) 2789.PubMedCrossRefGoogle Scholar
  18. 18.
    Weinstein, J.N., Yoshikami, S., Henkart, P., Blumenthal, R. and Hagins, W.A.: Biophys. J. 16 (1976) 104a.Google Scholar
  19. 19.
    Uemura, K., and Kinsky, S.C.: Biochemistry 11 (1972) 4085.PubMedCrossRefGoogle Scholar
  20. 20.
    Goldman, D.E.: J. Gen. Physiol. 27 (1943) 37.PubMedCrossRefGoogle Scholar
  21. 21.
    McLaughlin, S. and Eisenberg, M.: Annu. Rev. Biophys. & Bioeng. 4 (1975) 335.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • Robert Blumenthal
    • 1
  • John N. Weinstein
    • 1
  • Pierre Henkart
    • 2
  1. 1.Laboratory of Theoretical BiologyNational Institutes of Health, National Cancer InstituteBethesdaUSA
  2. 2.Immunology BranchNational Institutes of Health, National Cancer InstituteBethesdaUSA

Personalised recommendations