| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Central Laboratory of The Netherlands Red Cross Blood Transfusion Service and the Laboratory for Clinical and Experimental Immunology, and
Department of Internal Medicine, Renal Transplant Unit, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
Department of Research, Evanston Hospital, Northwestern University, Evanston, IL 60201;
§
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands;
¶
Department of Rheumatology, Daniel Den Hoed Clinic, Rotterdam, The Netherlands; and
||
Organon Technika, Boxtel, The Netherlands
Activated CTLs and NK cells induce apoptosis via multiple mechanisms, including that termed granule exocytosis. The latter pathway consists of vectorial secretion of perforin and a family of granule-associated serine proteases (granzymes) to the target cell. To establish whether granzymes are released extracellularly during cytolytic reactions in vivo, ELISAs that measure the native enzymes were developed and were found to specifically detect granzyme A (GrA) and granzyme B (GrB) at picogram concentrations. Low levels of GrA and GrB were present in plasma of healthy individuals (GrA, 33.5 pg/ml (median); GrB, 11.5 pg/ml (median)), whereas significantly higher levels were present in patients with ongoing CTL response, i.e., patients suffering from infections by EBV or HIV type 1. Markedly elevated levels were also noted in synovial fluid of patients with active rheumatoid arthritis. The measurement of soluble granzymes should be useful to assess clinical disorders associated with activated CTL and NK cells. Furthermore, these results suggest that granzymes mediate biologic effects beyond their described role in apoptotic cell death.
This article has been cited by other articles:
|
|
 |
|
  N. Melzer, S. G. Meuth, and H. Wiendl CD8+ T cells and neuronal damage: direct and collateral mechanisms of cytotoxicity and impaired electrical excitability FASEB J, November 1, 2009; 23(11): 3659 - 3673. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Martinvalet, M. Walch, D. K. Jensen, J. Thiery, and J. Lieberman Response: Granzyme A: cell death-inducing protease, proinflammatory agent, or both? Blood, October 29, 2009; 114(18): 3969 - 3970. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hagn, E. Schwesinger, V. Ebel, K. Sontheimer, J. Maier, T. Beyer, T. Syrovets, Y. Laumonnier, D. Fabricius, T. Simmet, et al. Human B Cells Secrete Granzyme B When Recognizing Viral Antigens in the Context of the Acute Phase Cytokine IL-21 J. Immunol., August 1, 2009; 183(3): 1838 - 1845. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Ngan, S. V. Vickerman, D. J. Granville, S. F. P. Man, and D. D. Sin The possible role of granzyme B in the pathogenesis of chronic obstructive pulmonary disease Therapeutic Advances in Respiratory Disease, June 1, 2009; 3(3): 113 - 129. [Abstract] [PDF]
|
|
|
|
|
|
T. Matsui, J. E. Connolly, M. Michnevitz, D. Chaussabel, C.-I Yu, C. Glaser, S. Tindle, M. Pypaert, H. Freitas, B. Piqueras, et al. CD2 Distinguishes Two Subsets of Human Plasmacytoid Dendritic Cells with Distinct Phenotype and Functions J. Immunol., June 1, 2009; 182(11): 6815 - 6823. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Klingstrom, J. Hardestam, M. Stoltz, B. Zuber, A. Lundkvist, S. Linder, and C. Ahlm Loss of cell membrane integrity in puumala hantavirus-infected patients correlates with levels of epithelial cell apoptosis and perforin. J. Virol., August 1, 2006; 80(16): 8279 - 8282. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Buzza, L. Zamurs, J. Sun, C. H. Bird, A. I. Smith, J. A. Trapani, C. J. Froelich, E. C. Nice, and P. I. Bird Extracellular Matrix Remodeling by Human Granzyme B via Cleavage of Vitronectin, Fibronectin, and Laminin J. Biol. Chem., June 24, 2005; 280(25): 23549 - 23558. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R Goldbach-Mansky, S Suson, R Wesley, C E Hack, H S El-Gabalawy, and P P Tak Raised granzyme B levels are associated with erosions in patients with early rheumatoid factor positive rheumatoid arthritis Ann Rheum Dis, May 1, 2005; 64(5): 715 - 721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. DE FOST, W. CHIERAKUL, K. PIMDA, A. M. DONDORP, N. J. WHITE, and T. VAN DER POLL ACTIVATION OF CYTOTOXIC LYMPHOCYTES IN PATIENTS WITH SCRUB TYPHUS Am J Trop Med Hyg, April 1, 2005; 72(4): 465 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Han, X. Xu, D. Baidal, J. Leith, C. Ricordi, R. Alejandro, and N. S. Kenyon Assessment of Cytotoxic Lymphocyte Gene Expression in the Peripheral Blood of Human Islet Allograft Recipients: Elevation Precedes Clinical Evidence of Rejection Diabetes, September 1, 2004; 53(9): 2281 - 2290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M C Kraan, J J Haringman, H Weedon, E C Barg, M D Smith, M J Ahern, T J M Smeets, F C Breedveld, and P P Tak T cells, fibroblast-like synoviocytes, and granzyme B+ cytotoxic cells are associated with joint damage in patients with recent onset rheumatoid arthritis Ann Rheum Dis, May 1, 2004; 63(5): 483 - 488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Gross, W. Koelch, A. DeMaio, N. Arispe, and G. Multhoff Cell Surface-bound Heat Shock Protein 70 (Hsp70) Mediates Perforin-independent Apoptosis by Specific Binding and Uptake of Granzyme B J. Biol. Chem., October 17, 2003; 278(42): 41173 - 41181. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. W. Kuijpers, M. Biezeveld, A. Achterhuis, I. Kuipers, J. Lam, C. E. Hack, A. E. Becker, and A. C. van der Wal Longstanding Obliterative Panarteritis in Kawasaki Disease: Lack of Cyclosporin A Effect Pediatrics, October 1, 2003; 112(4): 986 - 992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Mackewicz, B. Wang, S. Metkar, M. Richey, C. J. Froelich, and J. A. Levy Lack of the CD8+ cell anti-HIV factor in CD8+ cell granules Blood, July 1, 2003; 102(1): 180 - 183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Odeberg, H. Browne, S. Metkar, C. J. Froelich, L. Branden, D. Cosman, and C. Soderberg-Naucler The Human Cytomegalovirus Protein UL16 Mediates Increased Resistance to Natural Killer Cell Cytotoxicity through Resistance to Cytolytic Proteins J. Virol., April 15, 2003; 77(8): 4539 - 4545. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Hirst, M. S. Buzza, C. H. Bird, H. S. Warren, P. U. Cameron, M. Zhang, P. G. Ashton-Rickardt, and P. I. Bird The Intracellular Granzyme B Inhibitor, Proteinase Inhibitor 9, Is Up-Regulated During Accessory Cell Maturation and Effector Cell Degranulation, and Its Overexpression Enhances CTL Potency J. Immunol., January 15, 2003; 170(2): 805 - 815. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Strik, B. A. Bladergroen, D. Wouters, W. Kisiel, J. H. Hooijberg, A. R. Verlaan, P. L. Hordijk, P. Schneider, C. E. Hack, and J. A. Kummer Distribution of the Human Intracellular Serpin Protease Inhibitor 8 in Human Tissues J. Histochem. Cytochem., November 1, 2002; 50(11): 1443 - 1454. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Vermijlen, D. Luo, C. J Froelich, J. P. Medema, J. A. Kummer, E. Willems, F. Braet, and E. Wisse Hepatic natural killer cells exclusively kill splenic/blood natural killer-resistant tumor cells by the perforin/granzyme pathway J. Leukoc. Biol., October 1, 2002; 72(4): 668 - 676. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. da Silva, M. Brickelmaier, G. R. Majeau, Z. Li, L. Su, Y.-M. Hsu, and P. S. Hochman Alefacept, an Immunomodulatory Recombinant LFA-3/IgG1 Fusion Protein, Induces CD16 Signaling and CD2/CD16-Dependent Apoptosis of CD2+ Cells J. Immunol., May 1, 2002; 168(9): 4462 - 4471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Smyth, J. M. Kelly, V. R. Sutton, J. E. Davis, K. A. Browne, T. J. Sayers, and J. A. Trapani Unlocking the secrets of cytotoxic granule proteins J. Leukoc. Biol., July 1, 2001; 70(1): 18 - 29. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ogawa, K. Tanaka, A. Ishii, Y. Nakamura, S. Kondo, K. Sugamura, S. Takano, M. Nakamura, and K. Nagata A Novel Serum Protein That Is Selectively Produced by Cytotoxic Lymphocytes J. Immunol., May 15, 2001; 166(10): 6404 - 6412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Bladergroen, M. C. M. Strik, N. Bovenschen, O. van Berkum, G. L. Scheffer, C. J. L. M. Meijer, C. E. Hack, and J. A. Kummer The Granzyme B Inhibitor, Protease Inhibitor 9, Is Mainly Expressed by Dendritic Cells and at Immune-Privileged Sites J. Immunol., March 1, 2001; 166(5): 3218 - 3225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Tremblay, A. M. Wolbink, Y. Cormier, and C. E. Hack Granzyme Activity in the Inflamed Lung Is Not Controlled by Endogenous Serine Proteinase Inhibitors J. Immunol., October 1, 2000; 165(7): 3966 - 3969. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. N. Lauw, D. Pajkrt, C. E. Hack, M. Kurimoto, S. J. H. van Deventer, and T. van der Poll Proinflammatory Effects of IL-10 During Human Endotoxemia J. Immunol., September 1, 2000; 165(5): 2783 - 2789. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Baars, L. M. Ribeiro do Couto, J. H. W. Leusen, B. Hooibrink, T. W. Kuijpers, S. M. A. Lens, and R. A. W. van Lier Cytolytic Mechanisms and Expression of Activation-Regulating Receptors on Effector-Type CD8+CD45RA+CD27- Human T Cells J. Immunol., August 15, 2000; 165(4): 1910 - 1917. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. H. A. Spaeny-Dekking, A. M. Kamp, C. J. Froelich, and C. E. Hack Extracellular granzyme A, complexed to proteoglycans, is protected against inactivation by protease inhibitors Blood, February 15, 2000; 95(4): 1465 - 1472. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Wilharm, M. A. A. Parry, R. Friebel, H. Tschesche, G. Matschiner, C. P. Sommerhoff, and D. E. Jenne Generation of Catalytically Active Granzyme K from Escherichia coli Inclusion Bodies and Identification of Efficient Granzyme K Inhibitors in Human Plasma J. Biol. Chem., September 17, 1999; 274(38): 27331 - 27337. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
