Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Complement System01:27

Complement System

2.2K
The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a...
2.2K
Caspases01:24

Caspases

12.1K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
12.1K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

6.1K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.1K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

6.2K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.2K
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

833
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
833
Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

2.3K
Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult...
2.3K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

<i>SPP1</i><sup>hi</sup> macrophages in fibrin niches promote hyperplastic tissue remodeling in rheumatoid arthritis synovium.

Science translational medicine·2026
Same author

Functional and dysfunctional T regulatory cell states in human tissues in RA and other autoimmune arthritic diseases.

Nature immunology·2026
Same author

A multi-ethnic reference map of T cell receptor germline diversity reveals evidence of natural selection on alpha chain genes.

Nature communications·2026
Same author

scLASER: a robust framework for simulating and detecting time-dependent single-cell dynamics in longitudinal studies.

bioRxiv : the preprint server for biology·2026
Same author

CD25 expression marks an activated mast cell population in human nasal polyposis.

The Journal of allergy and clinical immunology·2026
Same author

Early and late RNA eQTL are driven by different genetic mechanisms.

Nature communications·2026
Same journal

Daily briefing: 'Cyborg' cockroaches breathe underwater with printed suit.

Nature·2026
Same journal

China boosts prestigious grants for young scientists - will it ease competition?

Nature·2026
Same journal

Incoming US science academy chief vows to 'double down' on research.

Nature·2026
Same journal

Author Correction: Synthesis of enantioenriched atropisomers by biocatalytic deracemization.

Nature·2026
Same journal

Electrodeposited self-assembled molecules for perovskite photovoltaics.

Nature·2026
Same journal

Neutrino's nursery found: the 'Shadow Blaster'.

Nature·2026
See all related articles

Related Experiment Video

Updated: May 29, 2025

A Colorimetric Assay that Specifically Measures Granzyme B Proteolytic Activity: Hydrolysis of Boc-Ala-Ala-Asp-S-Bzl
05:20

A Colorimetric Assay that Specifically Measures Granzyme B Proteolytic Activity: Hydrolysis of Boc-Ala-Ala-Asp-S-Bzl

Published on: November 28, 2014

13.1K

Granzyme K activates the entire complement cascade.

Carlos A Donado1, Erin Theisen1,2, Fan Zhang3

  • 1Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Nature
|February 6, 2025
PubMed
Summary
This summary is machine-generated.

Granzyme K (GZMK), a lymphocyte-derived enzyme, activates the complement cascade, driving inflammation in diseases like rheumatoid arthritis. Mice lacking GZMK show reduced inflammatory disease, highlighting GZMK

More Related Videos

A High Yield and Cost-efficient Expression System of Human Granzymes in Mammalian Cells
09:16

A High Yield and Cost-efficient Expression System of Human Granzymes in Mammalian Cells

Published on: June 10, 2015

9.8K
Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

9.0K

Related Experiment Videos

Last Updated: May 29, 2025

A Colorimetric Assay that Specifically Measures Granzyme B Proteolytic Activity: Hydrolysis of Boc-Ala-Ala-Asp-S-Bzl
05:20

A Colorimetric Assay that Specifically Measures Granzyme B Proteolytic Activity: Hydrolysis of Boc-Ala-Ala-Asp-S-Bzl

Published on: November 28, 2014

13.1K
A High Yield and Cost-efficient Expression System of Human Granzymes in Mammalian Cells
09:16

A High Yield and Cost-efficient Expression System of Human Granzymes in Mammalian Cells

Published on: June 10, 2015

9.8K
Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

9.0K

Area of Science:

  • Immunology
  • Protease function
  • Complement system biology

Background:

  • Granzymes are serine proteases primarily from cytotoxic lymphocytes.
  • Their role in cell death is established, but extracellular functions, including inflammation, are emerging.
  • Granzyme K (GZMK) is abundant in CD8+ T cells in rheumatoid arthritis synovium but its function is unclear.

Purpose of the Study:

  • To elucidate the function of Granzyme K (GZMK).
  • To investigate GZMK's role in activating the complement cascade.
  • To determine GZMK's contribution to inflammatory diseases.

Main Methods:

  • Biochemical assays to assess GZMK's cleavage of complement proteins C2 and C4.
  • Analysis of complement activation pathways in vitro.
  • In vivo studies using Gzmk-deficient mice to assess inflammatory disease phenotypes.
  • Immunohistochemical analysis of rheumatoid arthritis synovium.

Main Results:

  • GZMK directly cleaves complement proteins C4 and C2, initiating the complement cascade.
  • GZMK-mediated activation generates all complement effector molecules, including anaphylatoxins and the membrane attack complex.
  • GZMK is localized in areas of complement activation in rheumatoid arthritis synovium.
  • Gzmk-deficient mice exhibit significantly reduced arthritis and dermatitis, with decreased complement activation.

Conclusions:

  • GZMK is a novel activator of the classical complement cascade.
  • Lymphocyte-derived GZMK drives complement-mediated inflammation in chronic inflammatory diseases.
  • Targeting GZMK may offer a therapeutic strategy for inflammatory conditions.