TY - JOUR
T1 - Functional channel formation associated with cytotoxic T-cell granules
AU - Young, J. D.E.
AU - Nathan, C. F.
AU - Podack, E. R.
AU - Palladino, M. A.
AU - Cohn, Z. A.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1986
Y1 - 1986
N2 - Lymphocyte granules from cytotoxic T-lymphocyte lines A2, A11, and R8 were enriched by subcellular fractionation using a Percoll gradient. Granule-enriched fractions showed potent hemolytic activity in the presence of Ca2+. Isolated granules induced rapid Ca2+-dependent membrane depolarization of J774 macrophage-like cells. When tested in planar bilayers, granules induced the formation of Ca2+-dependent functional ion channels of large conductance steps of 1-6 nS in 0.1 M NaCl. Granule-induced channels were resistant to closing by an increase in transmembrane potential, with few channels shifting to the closed state only at voltages of >70 mV, following a Poisson process. These channels showed poor ion selectivity and were permeable to all monovalent and divalent ions (K+, Na+, Li+, Cl-, Ca2+, Mg2+, Zn2+, Ba2+). Ultrastructural examination of soluble granule proteins incubated for 48 hr at 37° C in the presence of Ca2+ revealed ring-like structures of 150-200 Å. Structural and functional channel formation may be involved in cytolysis induced by cytotoxic T lymphocytes.
AB - Lymphocyte granules from cytotoxic T-lymphocyte lines A2, A11, and R8 were enriched by subcellular fractionation using a Percoll gradient. Granule-enriched fractions showed potent hemolytic activity in the presence of Ca2+. Isolated granules induced rapid Ca2+-dependent membrane depolarization of J774 macrophage-like cells. When tested in planar bilayers, granules induced the formation of Ca2+-dependent functional ion channels of large conductance steps of 1-6 nS in 0.1 M NaCl. Granule-induced channels were resistant to closing by an increase in transmembrane potential, with few channels shifting to the closed state only at voltages of >70 mV, following a Poisson process. These channels showed poor ion selectivity and were permeable to all monovalent and divalent ions (K+, Na+, Li+, Cl-, Ca2+, Mg2+, Zn2+, Ba2+). Ultrastructural examination of soluble granule proteins incubated for 48 hr at 37° C in the presence of Ca2+ revealed ring-like structures of 150-200 Å. Structural and functional channel formation may be involved in cytolysis induced by cytotoxic T lymphocytes.
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U2 - 10.1073/pnas.83.1.150
DO - 10.1073/pnas.83.1.150
M3 - Article
C2 - 2417234
AN - SCOPUS:0022570037
VL - 83
SP - 150
EP - 154
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 1
ER -