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

Marcella Ferlito; Kaikobad Irani; Nauder Faraday; Charles J Lowenstein

doi:10.1073/pnas.0600275103

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

Journal article

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

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

Proceedings of the National Academy of Sciences - PNAS, Vol.103(31), pp.11689-11694

08/01/2006

DOI: 10.1073/pnas.0600275103

PMCID: PMC1544231

PMID: 16857739

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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 perforin: 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.

Biological Sciences

granzyme

inflammation

Ras

mitogen-activated protein kinases

lymphocyte

Details

Title: Subtitle: Nitric oxide inhibits exocytosis of cytolytic granules from lymphokine-activated killer cells
Creators: Marcella Ferlito - Departments of Medicine
Kaikobad Irani - Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213
Nauder Faraday - Anesthesiology, and
Charles J Lowenstein - Departments of Medicine
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.103(31), pp.11689-11694
DOI: 10.1073/pnas.0600275103
PMID: 16857739
PMCID: PMC1544231
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 08/01/2006
Academic Unit: Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
Record Identifier: 9984047715502771

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