The DOI matches its Crossref record; 235 of the 235 references it cites were found in a registry or an index.
Intracellular versus extracellular granzyme B in immunity and disease: challenging the dogma
Open accessAbstract
The cytotoxic granzyme B (GrB)/perforin pathway has been traditionally viewed as a primary mechanism that is used by cytotoxic lymphocytes to eliminate allogeneic, virally infected and/or transformed cells. Although originally proposed to have intracellular and extracellular functions, upon the discovery that perforin, in combination with GrB, could induce apoptosis, other potential functions for this protease were, for the most part, disregarded. As there are 5 granzymes in humans and 11 granzymes in mice, many studies used perforin knockout mice as an initial screen to evaluate the role of granzymes in disease. However, in recent years, emerging clinical and biochemical evidence has shown that the latter approach may have overlooked a critical perforin-independent, pathogenic role for these proteases in disease. This review focuses on GrB, the most characterized of the granzyme family, in disease. Long known to be a pro-apoptotic protease expressed by cytotoxic lymphocytes and natural killer cells, it is now accepted that GrB can be expressed in other cell types of immune and nonimmune origin. To the latter, an emerging immune-independent role for GrB has been forwarded due to recent discoveries that GrB may be expressed in nonimmune cells such as smooth muscle cells, keratinocytes, and chondrocytes in certain disease states. Given that GrB retains its activity in the blood, can cleave extracellular matrix, and its levels are often elevated in chronic inflammatory diseases, this protease may be an important contributor to certain pathologies. The implications of sustained elevations of intracellular and extracellular GrB in chronic vascular, dermatological, and neurological diseases, among others, are developing. This review examines, for the first time, the multiple roles of GrB in disease pathogenesis.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S. M., Ahmad, M., Alnemri, E. S., & Wang, X. (1997) · Cell · doi:10.1016/s0092-8674(00)80434-1 · Cited by 7,289
Hengartner, M. O. (2000) · Nature · doi:10.1038/35037710 · Cited by 5,779
WRITING GROUP MEMBERS, Lloyd-Jones, D., Adams, R., Carnethon, M., De Simone, G., Ferguson, T. B., Flegal, K., Ford, E., Furie, K., Go, A., et al. (2009) · Circulation · doi:10.1161/circulationaha.108.191259 · Cited by 3,908
The Nature of Small-Airway Obstruction in Chronic Obstructive Pulmonary Disease
Hogg, J. C., Chu, F., Utokaparch, S., Woods, R., Elliott, W. M., Buzatu, L., Cherniack, R. M., Rogers, R. M., Sciurba, F. C., Coxson, H. O., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa032158 · Cited by 3,782
The immune response in atherosclerosis: a double-edged sword
Hansson, G. K., & Libby, P. (2006) · Nature Reviews Immunology · doi:10.1038/nri1882 · Cited by 2,182
Fox, R. I. (2005) · The Lancet · doi:10.1016/s0140-6736(05)66990-5 · Cited by 1,828
The Receptor for the Cytotoxic Ligand TRAIL
Pan, G., O'Rourke, K., Chinnaiyan, A. M., Gentz, R., Ebner, R., Ni, J., & Dixit, V. M. (1997) · Science · doi:10.1126/science.276.5309.111 · Cited by 1,767
Kebir, H., Kreymborg, K., Ifergan, I., Dodelet-Devillers, A., Cayrol, R., Bernard, M., Giuliani, F., Arbour, N., Becher, B., & Prat, A. (2007) · Nature Medicine · doi:10.1038/nm1651 · Cited by 1,759
Kägi, D., Ledermann, B., Bürki, K., Seiler, P., Odermatt, B., Olsen, K. J., Podack, E. R., Zinkernagel, R. M., & Hengartner, H. (1994) · Nature · doi:10.1038/369031a0 · Cited by 1,757
Casciola-Rosen, L. A., Anhalt, G., & Rosen, A. (1994) · The Journal of experimental medicine · doi:10.1084/jem.179.4.1317 · Cited by 1,717
Cited by
Senescent cells: an emerging target for diseases of ageing
Childs, B. G., Gluscevic, M., Baker, D. J., Laberge, R.-M., Marquess, D., Dananberg, J., & van Deursen, J. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.116 · Cited by 1,284
Cauwe, B., & Opdenakker, G. (2010) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2010.501783 · Cited by 299
Śledzińska, A., Vila de Mucha, M., Bergerhoff, K., Hotblack, A., Demane, D. F., Ghorani, E., Akarca, A. U., Marzolini, M. A. V., Solomon, I., Vargas, F. A., et al. (2020) · Immunity · doi:10.1016/j.immuni.2019.12.007 · Cited by 228
Chen, X., Zhao, J., Yue, S., Li, Z., Duan, X., Lin, Y., Yang, Y., He, J., Gao, L., Pan, Z., et al. (2024) · Nature Cancer · doi:10.1038/s43018-024-00760-x · Cited by 68
Ang, L. S., Boivin, W. A., Williams, S. J., Zhao, H., Abraham, T., Carmine-Simmen, K., McManus, B. M., Bleackley, R. C., & Granville, D. J. (2011) · Cell Death & Disease · doi:10.1038/cddis.2011.88 · Cited by 55
Self-citation
Metadata
- Authors
- Boivin, W. A., Cooper, D. M., Hiebert, P. R., & Granville, D. J.
- Venue
- Laboratory Investigation
- Publisher
- Elsevier BV
- Published
- 2009-11
- Volume
- 89
- Issue
- 11
- Pages
- 1195-1220
- ISSN
- 0023-6837 (ISSN-L)
- OpenAlex
- W2012110635
- Cited by
- 314
- References
- 235
- FWCI
- 5.28
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Intracellular versus extracellular granzyme B in immunity and disease: challenging the dogma. https://app.cochat.ai/papers/10.1038/labinvest.2009.91
- The paper
- Boivin, W. A., Cooper, D. M., Hiebert, P. R., & Granville, D. J. (2009). Intracellular versus extracellular granzyme B in immunity and disease: challenging the dogma. Laboratory Investigation. https://doi.org/10.1038/labinvest.2009.91
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
