Role of the inflammatory protein serine protease inhibitor Kazal in preventing cytolytic granule granzyme A-mediated apoptosis.

Felix Lu, Jason Lamontagne, Angela Sun, Mark Pinkerton, Timothy Block, Xuanyong Lu

Drexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, College of Medicine, Drexel University, Doylestown, PA 18902, USA.

Immunology 2011 Dec

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Serine protease inhibitor Kazal (SPIK) is an inflammatory protein whose levels are elevated in numerous cancers. However, the role of this protein in cancer development is unknown. We have recently found that SPIK suppresses serine protease-dependent cell apoptosis. Here, we report that anti-SPIK antibodies can co-immmunoprecipitate serine protease granzyme A (GzmA), a cytolytic granule secreted by cytotoxic T lymphocytes and natural killer cells during immune surveillance, and that SPIK suppresses GzmA-induced cell apoptosis. Deletion studies show that the C3-C4 region of SPIK is critical for this suppression. These studies suggest that over-expression of SPIK may prevent GzmA-mediated immune-killing, thereby establishing the tolerance of cancer cells to the body's immune surveillance system. Suppression of over-expressed SPIK can restore the susceptibility of these cells to apoptotic death triggered by GzmA. This finding implies that it is possible to overcome tolerance of cancer cells to the body's immune surveillance system and restore the GzmA-mediated immune-killing by suppressing the over-expression of SPIK. © 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd.

Citation

Felix Lu, Jason Lamontagne, Angela Sun, Mark Pinkerton, Timothy Block, Xuanyong Lu. Role of the inflammatory protein serine protease inhibitor Kazal in preventing cytolytic granule granzyme A-mediated apoptosis. Immunology. 2011 Dec;134(4):398-408