15 kDa granulysin causes differentiation of monocytes to dendritic cells but lacks cytotoxic activity.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Carol ClaybergerA M Krensky

Abstract

Granulysin is expressed as two isoforms by human cytotoxic cells: a single mRNA gives rise to 15 kDa granulysin, a portion of which is cleaved to a 9 kDa protein. Studies with recombinant 9 kDa granulysin have demonstrated its cytolytic and proinflammatory properties, but much less is known about the biologic function of the 15 kDa isoform. In this study, we show that the subcellular localization and functions of 9 and 15 kDa granulysin are largely distinct. Nine kilodalton granulysin is confined to cytolytic granules that are directionally released following target cell recognition. In contrast, 15 kDa granulysin is located in distinct granules that lack perforin and granzyme B and that are released by activated cytolytic cells. Although recombinant 9 kDa granulysin is cytolytic against a variety of tumors and microbes, recombinant 15 kDa granulysin is not. The 15 kDa isoform is a potent inducer of monocytic differentiation to dendritic cells, but the 9 kDa isoform is not. In vivo, mice expressing granulysin show markedly improved antitumor responses, with increased numbers of activated dendritic cells and cytokine-producing T cells. Thus, the distinct functions of granulysin isoforms have major implications for diagnosis and ...Continue Reading

References

Mar 1, 1987·The Journal of Experimental Medicine·J JongstraA M Krensky
May 5, 1995·The Journal of Biological Chemistry·P S TobiasR J Ulevitch
Nov 14, 1997·The Journal of Experimental Medicine·D HamannR A van Lier
Jun 8, 1999·The Journal of Experimental Medicine·R ShimazuM Kimoto
Aug 17, 1999·Molecular Immunology·D A HansonA M Krensky
Jun 22, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·A A KasparA M Krensky
Feb 6, 2002·The Journal of Experimental Medicine·Franca GerosaGiorgio Trinchieri
Feb 6, 2002·The Journal of Experimental Medicine·Diego PiccioliNicholas M Valiante
Jul 30, 2003·European Journal of Immunology·Kazuyuki OgawaKinya Nagata
Nov 6, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nicola DalbethMargaret F C Callan
Jun 16, 2005·Current Opinion in Immunology·Joost J Oppenheim, De Yang
Dec 24, 2005·The New England Journal of Medicine·Franck PagèsJérôme Galon
Jun 13, 2006·Current Opinion in Immunology·Melissa B Lodoen, Lewis L Lanier
Oct 24, 2006·Nature Immunology·Stefan WelteAlexander Steinle
Dec 22, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lisa P HuangAlan M Krensky
Jul 14, 2007·Blood·Angela L ZhangKalle Söderström
Aug 11, 2007·Journal of Gastroenterology and Hepatology·Susumu SaigusaHidetaka Mochizuki
Jan 15, 2008·International Journal of Hematology·Masayuki NagasawaShuki Mizutani
Sep 19, 2008·Immunity·Cornelis J M Melief
Jan 28, 2009·Nature Reviews. Immunology·Jordan S Orange
Apr 29, 2009·Expert Review of Vaccines·Xiaochuan ChenDavid M Goldenberg
Oct 7, 2009·Annals of Internal Medicine·Riichiro AbeHiroshi Shimizu
Dec 8, 2009·Blood·Molly A IngersollGwendalyn J Randolph
Jul 17, 2010·Nature Reviews. Immunology·Geneviève de Saint BasileAlain Fischer
Aug 3, 2010·Protein Expression and Purification·Michael W FinnAlan M Krensky
Feb 8, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Reena V SainiCarol Clayberger
Apr 20, 2011·Journal of Translational Medicine·Luciano CastielloMarianna Sabatino

❮ Previous
Next ❯

Citations

Nov 15, 2012·Immunotherapy·David F Stroncek, Francisco M Marincola
Sep 26, 2015·Oncoimmunology·Sameer Al-WasabyAlberto Anel
Mar 3, 2018·International Journal of Environmental Research and Public Health·Gaurav SharmaU M H Aqil
May 19, 2018·American Journal of Reproductive Immunology : AJRI·Tamara GulicDaniel Rukavina
Aug 9, 2012·Asia Pacific Allergy·Hideo Hashizume
Jan 29, 2019·American Journal of Reproductive Immunology : AJRI·Koushi Yamaguchi
Nov 23, 2017·Frontiers in Immunology·Patricia PereiroBeatriz Novoa
May 27, 2016·American Journal of Reproductive Immunology : AJRI·Tamara GulicDaniel Rukavina
Mar 15, 2016·American Journal of Reproductive Immunology : AJRI·Marin DominovicDaniel Rukavina
Oct 28, 2019·Oncoimmunology·Raquel Ibáñez-PérezAlberto Anel
Jun 30, 2015·Scandinavian Journal of Immunology·M LettauO Janssen
Mar 27, 2021·Cancer Treatment and Research Communications·Sameer Al-WasabyAlberto Anel

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cell Adhesion Molecules in the Brain

Cell adhesion molecules found on cell surface help cells bind with other cells or the extracellular matrix to maintain structure and function. Here is the latest research on their role in the brain.