Lipid Model Membrane Studies on Immune Cytotoxic Mechanisms
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.
KeywordsConductance Increase Conductance Change Phosphatidyl Ethanolamine Planar Lipid Bilayer Target Cell Membrane
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