Granzyme serine proteases in inflammation and rheumatic diseases.
Nat Rev Rheumatol
; 20(6): 361-376, 2024 Jun.
Article
in En
| MEDLINE
| ID: mdl-38689140
ABSTRACT
Granzymes (granule-secreted enzymes) are a family of serine proteases that have been viewed as redundant cytotoxic enzymes since their discovery more than 30 years ago. Predominantly produced by cytotoxic lymphocytes and natural killer cells, granzymes are delivered into the cytoplasm of target cells through immunological synapses in cooperation with the pore-forming protein perforin. After internalization, granzymes can initiate cell death through the cleavage of intracellular substrates. However, evidence now also demonstrates the existence of non-cytotoxic, pro-inflammatory, intracellular and extracellular functions that are granzyme specific. Under pathological conditions, granzymes can be produced and secreted extracellularly by immune cells as well as by non-immune cells. Depending on the granzyme, accumulation in the extracellular milieu might contribute to inflammation, tissue injury, impaired wound healing, barrier dysfunction, osteoclastogenesis and/or autoantigen generation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Rheumatic Diseases
/
Granzymes
/
Inflammation
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Rev Rheumatol
Journal subject:
REUMATOLOGIA
Year:
2024
Document type:
Article