Identification of low molecular weight probes on perforin- and Fas-based killing mediated by cytotoxic T lymphocytes.
Perforin- and Fas-based killing pathways are two major mechanisms of cytotoxic T lymphocytes (CTL)-mediated cytotoxicity. In this paper, we have reported the identification of low molecular weight probes on CTL-mediated cytolysis. In addition to inhibitors of acidification so far reported, three other groups of compounds have been identified to block perforin-based cytolysis by the CD8+ CTL clone: (1) an inhibitor of actin polymerization (cytochalasin D), (2) respiratory inhibitors (antimycin A and oligomycin A), and (3) protein kinase inhibitors (calphostin C, herbimycin A, K252a, and staurosporine). Since Fas-based cytolysis by CD4+ CTL clone was inhibitable or rather increased by these agents, only vacuolar type H(+)-ATPase inhibitors such as concanamycin A have been shown to be highly specific probes to block perforin-based CTL-mediated cytotoxicity.
Kataoka
T
T
Department of Bioengineering, Tokyo Institute of Technology, Yokohama, Japan.
Taniguchi
M
M
Yamada
A
A
Suzuki
H
H
Hamada
S
S
Magae
J
J
Nagai
K
K
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018942:Macrolides; D008562:Membrane Glycoproteins / Q000502:physiology*; D015335:Molecular Probes; D008970:Molecular Weight; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014617:Vacuoles / Q000201:enzymology; D019014:fas Receptor / Q000276:immunology*
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D018942:Macrolides; D008562:Membrane Glycoproteins; D015335:Molecular Probes; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor; D054353:Perforin; C036978:concanamycin A; D006180:Proton-Translocating ATPases