C J Froelich

Summary

Affiliation: Northwestern University
Country: USA

Publications

  1. pmc Granzyme B activates procaspase-3 which signals a mitochondrial amplification loop for maximal apoptosis
    Sunil S Metkar
    Evanston Northwestern Healthcare Research Institute, Feinberg School of Medicine, Northwestern University, Evanston, IL 60201, USA
    J Cell Biol 160:875-85. 2003
  2. ncbi request reprint Right place, right time
    Christopher J Froelich
    Evanston Northwestern Healthcare Research Institute, Evanston, IL 60201, USA
    Nat Immunol 5:124-5. 2004
  3. doi request reprint Granule-associated serine proteases: granzymes might not just be killer proteases
    Christopher J Froelich
    Department of Medicine, NorthShore University HealthSystem Research Institute, Evanston, IL, 60201, USA
    Trends Immunol 30:117-23. 2009
  4. ncbi request reprint Granzyme B-mediated apoptosis--the elephant and the blind men?
    C J Froelich
    Department of Medicine, Evanston Northwestern Healthcare Research Institute, Evanston, IL 60201, USA
    Cell Death Differ 11:369-71. 2004
  5. ncbi request reprint Apoptosis induced by granzyme B-glycosaminoglycan complexes: implications for granule-mediated apoptosis in vivo
    J P Galvin
    Evanston Northwestern Healthcare Research Institute, Northwestern University, IL 60201, USA
    J Immunol 162:5345-50. 1999
  6. ncbi request reprint New paradigm for lymphocyte granule-mediated cytotoxicity. Target cells bind and internalize granzyme B, but an endosomolytic agent is necessary for cytosolic delivery and subsequent apoptosis
    C J Froelich
    Department of Medicine, Evanston Hospital, Northwestern University, Evanston, Illinois 60201, USA
    J Biol Chem 271:29073-9. 1996
  7. ncbi request reprint Cytotoxic granule-mediated apoptosis: unraveling the complex mechanism
    Srikumar M Raja
    Department of Medicine, Evanston Northwestern Healthcare Research Institute, 2650 Ridge Avenue, Evanston, IL 60201, USA
    Curr Opin Immunol 15:528-32. 2003
  8. ncbi request reprint Granzyme B/perforin-mediated apoptosis of Jurkat cells results in cleavage of poly(ADP-ribose) polymerase to the 89-kDa apoptotic fragment and less abundant 64-kDa fragment
    C J Froelich
    Department of Medicine, Evanston Hospital, Northwestern University, Illinois 60201, USA
    Biochem Biophys Res Commun 227:658-65. 1996
  9. ncbi request reprint Cytotoxic cell granule-mediated apoptosis: perforin delivers granzyme B-serglycin complexes into target cells without plasma membrane pore formation
    Sunil S Metkar
    Evanston Northwestern Healthcare Research Institute, Evanston, IL 60201, USA
    Immunity 16:417-28. 2002
  10. ncbi request reprint Cytotoxic cell granule-mediated apoptosis. Characterization of the macromolecular complex of granzyme B with serglycin
    Srikumar M Raja
    Department of Medicine, Evanston Northwestern Healthcare Research Institute, 2650 Ridge Avenue, Evanston, Illinois 60201, USA
    J Biol Chem 277:49523-30. 2002

Collaborators

Detail Information

Publications31

  1. pmc Granzyme B activates procaspase-3 which signals a mitochondrial amplification loop for maximal apoptosis
    Sunil S Metkar
    Evanston Northwestern Healthcare Research Institute, Feinberg School of Medicine, Northwestern University, Evanston, IL 60201, USA
    J Cell Biol 160:875-85. 2003
    ....
  2. ncbi request reprint Right place, right time
    Christopher J Froelich
    Evanston Northwestern Healthcare Research Institute, Evanston, IL 60201, USA
    Nat Immunol 5:124-5. 2004
  3. doi request reprint Granule-associated serine proteases: granzymes might not just be killer proteases
    Christopher J Froelich
    Department of Medicine, NorthShore University HealthSystem Research Institute, Evanston, IL, 60201, USA
    Trends Immunol 30:117-23. 2009
    ....
  4. ncbi request reprint Granzyme B-mediated apoptosis--the elephant and the blind men?
    C J Froelich
    Department of Medicine, Evanston Northwestern Healthcare Research Institute, Evanston, IL 60201, USA
    Cell Death Differ 11:369-71. 2004
  5. ncbi request reprint Apoptosis induced by granzyme B-glycosaminoglycan complexes: implications for granule-mediated apoptosis in vivo
    J P Galvin
    Evanston Northwestern Healthcare Research Institute, Northwestern University, IL 60201, USA
    J Immunol 162:5345-50. 1999
    ..Collectively, the results indicate that neutral, high m.w. GrB has the capacity to induce cell death and will be useful to study the mechanism of cytotoxic cell-mediated apoptosis in vitro...
  6. ncbi request reprint New paradigm for lymphocyte granule-mediated cytotoxicity. Target cells bind and internalize granzyme B, but an endosomolytic agent is necessary for cytosolic delivery and subsequent apoptosis
    C J Froelich
    Department of Medicine, Evanston Hospital, Northwestern University, Evanston, Illinois 60201, USA
    J Biol Chem 271:29073-9. 1996
    ..These results indicate that adenovirus-mediated delivery of granzyme B is suitable for elucidating biochemical events that accompany granule-mediated apoptosis...
  7. ncbi request reprint Cytotoxic granule-mediated apoptosis: unraveling the complex mechanism
    Srikumar M Raja
    Department of Medicine, Evanston Northwestern Healthcare Research Institute, 2650 Ridge Avenue, Evanston, IL 60201, USA
    Curr Opin Immunol 15:528-32. 2003
    ..Recent evidence indicates that the physiological apoptosis-inducing form is a multi-component macro-complex consisting of cationic granule proteins non-covalently linked to the chondroitin-sulfate proteoglycan, serglycin...
  8. ncbi request reprint Granzyme B/perforin-mediated apoptosis of Jurkat cells results in cleavage of poly(ADP-ribose) polymerase to the 89-kDa apoptotic fragment and less abundant 64-kDa fragment
    C J Froelich
    Department of Medicine, Evanston Hospital, Northwestern University, Illinois 60201, USA
    Biochem Biophys Res Commun 227:658-65. 1996
    ..Intracellular granzyme B appears to be translocated to the nucleus where the protease directly cleaves poly(ADP-ribose) polymerase...
  9. ncbi request reprint Cytotoxic cell granule-mediated apoptosis: perforin delivers granzyme B-serglycin complexes into target cells without plasma membrane pore formation
    Sunil S Metkar
    Evanston Northwestern Healthcare Research Institute, Evanston, IL 60201, USA
    Immunity 16:417-28. 2002
    ....
  10. ncbi request reprint Cytotoxic cell granule-mediated apoptosis. Characterization of the macromolecular complex of granzyme B with serglycin
    Srikumar M Raja
    Department of Medicine, Evanston Northwestern Healthcare Research Institute, 2650 Ridge Avenue, Evanston, Illinois 60201, USA
    J Biol Chem 277:49523-30. 2002
    ..These studies provide a firm biophysical basis for our earlier reported observations that the proapoptotic granzyme is exocytosed predominantly as a macromolecular complex with SG...
  11. ncbi request reprint A novel mechanism for protein delivery: granzyme B undergoes electrostatic exchange from serglycin to target cells
    Srikumar M Raja
    Department of Medicine, Evanston Northwestern Healthcare Research Institute, Evanston, Illinois 60201, USA
    J Biol Chem 280:20752-61. 2005
    ..A mechanism of delivery is proposed entailing electrostatic transfer of granzyme B from serglycin to cell surface proteins...
  12. ncbi request reprint Granzyme B mimics apical caspases. Description of a unified pathway for trans-activation of executioner caspase-3 and -7
    X Yang
    Evanston Northwestern Healthcare Research Institute, Evanston, Illinois 60201, USA
    J Biol Chem 273:34278-83. 1998
    ..As a consequence, two proteases, caspase-3 and GrB, are required to activate procaspase-7...
  13. ncbi request reprint Detection of functional cell surface perforin by flow cytometry
    Sunil S Metkar
    Division of Rheumatology, Department of Medicine, ENH Research Institute and Northwestern University Feinberg School of Medicine, Evanston, IL 60201, USA
    J Immunol Methods 299:117-27. 2005
    ..Further, the variable sensitivity of effector versus target cell lines to the permeabilizing effects of PFN could not be attributed to differential binding of PFN...
  14. pmc Perforin oligomers form arcs in cellular membranes: a locus for intracellular delivery of granzymes
    S S Metkar
    NorthShore University Health Systems Research Institute and University of Chicago, Evanston, IL, USA
    Cell Death Differ 22:74-85. 2015
    ..The role of these arcs in PFN-mediated pathology warrants evaluation where they may serve as novel therapeutic targets. ..
  15. ncbi request reprint An antimicrobial activity of cytolytic T cells mediated by granulysin
    S Stenger
    Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90095, USA
    Science 282:121-5. 1998
    ..The ability of CTLs to kill intracellular M. tuberculosis was dependent on the presence of granulysin in cytotoxic granules, defining a mechanism by which T cells directly contribute to immunity against intracellular pathogens...
  16. ncbi request reprint Human perforin: rapid enrichment by immobilized metal affinity chromatography (IMAC) for whole cell cytotoxicity assays
    C J Froelich
    Department of Medicine, Evanston Hospital, Northwestern University, Evanston, Illinois 60201, USA
    Biochem Biophys Res Commun 229:44-9. 1996
    ..In addition to demonstrating the lytic activity of human perforin toward various cell lines, we show that the conditions of the cytotoxicity assay influence both the kinetics and magnitude of perforin-mediated cytotoxicity...
  17. doi request reprint Human and mouse granzyme A induce a proinflammatory cytokine response
    Sunil S Metkar
    Department of Medicine, NorthShore University HealthSystem Research Institute, Evanston, IL 60201, USA
    Immunity 29:720-33. 2008
    ..Thus, the granule secretory pathway plays an unexpected role in inflammation, with GzmA acting as an endogenous modulator...
  18. ncbi request reprint Lack of the CD8+ cell anti-HIV factor in CD8+ cell granules
    Carl E Mackewicz
    Rheumatology Research Laboratory, Women s Hospital, Evanston Northwestern Healthcare, Evanston, IL, USA
    Blood 102:180-3. 2003
    ..These findings suggest that CAF does not reside at appreciable levels in the exocytic granules of antiviral CD8+ T cells...
  19. pmc A clathrin/dynamin- and mannose-6-phosphate receptor-independent pathway for granzyme B-induced cell death
    Joseph A Trapani
    Cancer Immunology Laboratory, Peter MacCallum Cancer Institute, Melbourne 8006, Australia
    J Cell Biol 160:223-33. 2003
    ..Entry of granzyme B into target cells and its intracellular trafficking to induce target cell death in the presence of perforin are therefore not critically dependent on MPR or clathrin/dynamin-dependent endocytosis...
  20. ncbi request reprint NK cell protease granzyme M targets alpha-tubulin and disorganizes the microtubule network
    Niels Bovenschen
    Department of Pathology, University Medical Center, Utrecht University, Utrecht, The Netherlands
    J Immunol 180:8184-91. 2008
    ..We conclude that GrM targets major components of the cytoskeleton that likely contribute to NK cell-induced cell death...
  21. ncbi request reprint SPI-CI and SPI-6 cooperate in the protection from effector cell-mediated cytotoxicity
    Michael Bots
    Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, PO Box 9600, 2300 RC, Leiden, The Netherlands
    Blood 105:1153-61. 2005
    ..Our data therefore indicate that SPI-CI is a novel immune escape molecule that acts in concert with SPI-6 to prevent cytotoxic lymphocyte-mediated killing of tumor cells...
  22. ncbi request reprint A role for the granzyme B inhibitor serine protease inhibitor 6 in CD8+ memory cell homeostasis
    Tiphanie Phillips
    Committees on Immunology and Developmental Biology, Department of Pathology, Ben May Institute for Cancer Research, Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637, USA
    J Immunol 173:3801-9. 2004
    ..We propose that expression of protective molecules, like Spi6, serves to shield metabolically active CD8+ memory T cells from their own effector molecules...
  23. ncbi request reprint Degradation of Mcl-1 by granzyme B: implications for Bim-mediated mitochondrial apoptotic events
    Jie Han
    Departments of Pathology and Plastic Surgery, The University of Pittsburgh School of Medicine and The University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA
    J Biol Chem 279:22020-9. 2004
    ..The findings presented herein imply that Mcl-1L degradation by either GrB or caspase-3 interferes with Bim sequestration by Mcl-1L...
  24. ncbi request reprint Granzyme-mediated cytotoxicity does not involve the mannose 6-phosphate receptors on target cells
    Ralf Dressel
    Division of Immunogenetics, University of Gottingen, Heinrich Düker Weg 12, 37073 Gottingen, Germany
    J Biol Chem 279:20200-10. 2004
    ..In conclusion, these results strongly argue against an Mpr300- or Mpr46-dependent pathway of granzyme-mediated killing and provide new insight in the internalization of monomeric and complexed granzyme B...
  25. ncbi request reprint Modulation of the tumor cell phenotype by IFN-gamma results in resistance of uveal melanoma cells to granule-mediated lysis by cytotoxic lymphocytes
    Kristian Hallermalm
    Cancer Centrum Karolinska, Karolinska Institutet, Stockholm, Sweden
    J Immunol 180:3766-74. 2008
    ....
  26. pmc The human cytomegalovirus protein UL16 mediates increased resistance to natural killer cell cytotoxicity through resistance to cytolytic proteins
    Jenny Odeberg
    Department of Medicine, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden
    J Virol 77:4539-45. 2003
    ..Thus, the UL16 protein mediates an increased protection against the action of cytolytic proteins released by activated NK cells, possibly by a membrane-stabilizing mechanisms, rather than by delivering negative signals to NK cells...
  27. ncbi request reprint Extracellular matrix remodeling by human granzyme B via cleavage of vitronectin, fibronectin, and laminin
    Marguerite S Buzza
    Department of Biochemistry and Molecular Biology, Monash University, Clayton 3800, Australia
    J Biol Chem 280:23549-58. 2005
    ..It may also contribute to tissue destruction in diseases in which extracellular GrB is evident, such as rheumatoid arthritis and atherosclerosis...
  28. ncbi request reprint Hepatic natural killer cells exclusively kill splenic/blood natural killer-resistant tumor cells by the perforin/granzyme pathway
    David Vermijlen
    Laboratory for Cell Biology and Histology, Vrije Universiteit Brussel, Brussels, Belgium
    J Leukoc Biol 72:668-76. 2002
    ..Serine protease inhibitor PI-9/SPI-6 expression in liver sinusoidal endothelial cells may protect the liver microenvironment from this highly active perforin/granzyme pathway used to kill metastasizing cancer cells...
  29. ncbi request reprint Myeloma cells are highly sensitive to the granule exocytosis pathway mediated by WT1-specific cytotoxic T lymphocytes
    Taichi Azuma
    First Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan
    Clin Cancer Res 10:7402-12. 2004
    ..Because WT1 is a universal tumor antigen, we examined the sensitivity of myeloma cells to WT1-specific cytotoxic T lymphocyte (CTL)-mediated cytotoxicity...
  30. ncbi request reprint Reconstitution of caspase-3 confers low glucose-enhanced tumor necrosis factor-related apoptosis-inducing ligand cytotoxicity and Akt cleavage
    Yong J Lee
    Department of Surgery and Pharmacology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Clin Cancer Res 10:1894-900. 2004
    ..In this study, we used caspase-3-deficient MCF-7 breast cancer cells to examine the possible role of caspase-3 in glucose deprivation-enhanced TRAIL cytotoxicity...
  31. ncbi request reprint Human neutrophils lack granzyme A, granzyme B, and perforin
    Sunil S Metkar
    Blood 104:905-6; author reply 907-8. 2004