Identification of low molecular weight probes on perforin- and Fas-based killing mediated by cytotoxic T lymphocytes

Biosci Biotechnol Biochem. 1996 Oct;60(10):1726-8. doi: 10.1271/bbb.60.1726.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Cell Line
  • Cell Survival / immunology
  • Enzyme Inhibitors / pharmacology
  • Macrolides*
  • Membrane Glycoproteins / physiology*
  • Molecular Probes
  • Molecular Weight
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • Proton-Translocating ATPases / antagonists & inhibitors
  • T-Lymphocytes, Cytotoxic / immunology*
  • Vacuoles / enzymology
  • fas Receptor / immunology*

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Macrolides
  • Membrane Glycoproteins
  • Molecular Probes
  • Pore Forming Cytotoxic Proteins
  • fas Receptor
  • Perforin
  • concanamycin A
  • Proton-Translocating ATPases