Cell-mediated cytotoxicity and the reorientation of effector cell granules towards the target cell are inhibited by the protonophore carbonylcyanide m-chlorophenylhydrazone.
Cell-mediated cytotoxicity involves a localized secretory process in which lytic agents stored in specialized granules of the effector cells are released upon contact with the appropriate target cell membrane and cause membrane damage. The protonophore carbonylcyanide m-chlorophenylhydrazone (CCCP) inhibits cytotoxicity of natural killer cells, cytotoxic T-lymphocytes and lymphokine-activated killer cells. This inhibition is due to an effect of CCCP on the cytolytic cells, rather than on their targets, and is reversible. Treatment with CCCP does not inhibit the formation of effector-target conjugates, but seems to affect the programming of the effector cells for lysis. CCCP only inhibits lysis if added during a certain period of the lytic cycle: it has an effect only if added before, or within 5 minutes of the initiation of killing by a pulse of Ca++. Effector cells treated with CCCP retain their characteristic beta-glucuronidase-positive granules, but in the presence of the drug, these are no longer oriented to face the contact area with the target cell membrane.
McKinnon
K P
KP
Department of Microbiology and Immunology, Duke University Medical Center, Durham, North Carolina 27710.
Dunlevy
J R
JR
Dawson
J R
JR
Argon
Y
Y
D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology*; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D009570:Nitriles / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology
D009570:Nitriles; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone