Nitric oxide inhibits exocystosis of cytolytic granules from lymphokine-activated killer cells

Marcella Ferlito, Kaikobad Irani, Nauder Faraday, Charles J. Lowenstein

Research output: Contribution to journalArticlepeer-review

Abstract

NO inhibits cytotoxic T lymphocyte killing of target cells, although the precise mechanism is unknown. We hypothesized that NO decreases exocytosis of cytotoxic granules from activated lymphocytes. We now show that NO inhibits lymphokine-activated killer cell killing of K562 target cells. Exogenous and endogenous NO decreases the release of granzyme B, granzyme A, and perform: all contents of cytotoxic granules. NO inhibits the signal transduction cascade initiated by cross-linking of the T cell receptor that leads to granule exocytosis. In particular, we found that NO decreases the expression of Ras, a critical signaling component within the exocytic pathway. Ectopic expression of Ras prevents NO inhibition of exocytosis. Our data suggest that Ras mediates NO inhibition of lymphocyte cytotoxicity and emphasize that alterations in the cellular redox state may regulate the exocytic signaling pathway.

Original languageEnglish (US)
Pages (from-to)11689-11694
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number31
DOIs
StatePublished - Aug 1 2006

Keywords

  • Granzyme
  • Inflammation
  • Lymphocyte
  • Mitogen-activated protein kinases
  • Ras

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Nitric oxide inhibits exocystosis of cytolytic granules from lymphokine-activated killer cells'. Together they form a unique fingerprint.

Cite this