Work

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

Year: 2006

Type: article

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.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.0600275103

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

Institutions: Johns Hopkins University, Johns Hopkins Medicine, University of Pittsburgh Medical Center

Language: English

Topic: Immune Cell Function and Interaction

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green