Granzyme B promotes cytotoxic lymphocyte transmigration via basement membrane remodeling.
Immunity
; 41(6): 960-72, 2014 Dec 18.
Article
in En
| MEDLINE
| ID: mdl-25526309
ABSTRACT
Granzyme B (GzmB) is a protease with a well-characterized intracellular role in targeted destruction of compromised cells by cytotoxic lymphocytes. However, GzmB also cleaves extracellular matrix components, suggesting that it influences the interplay between cytotoxic lymphocytes and their environment. Here, we show that GzmB-null effector T cells and natural killer (NK) cells exhibited a cell-autonomous homing deficit in mouse models of inflammation and Ectromelia virus infection. Intravital imaging of effector T cells in inflamed cremaster muscle venules revealed that GzmB-null cells adhered normally to the vessel wall and could extend lamellipodia through it but did not cross it efficiently. In vitro migration assays showed that active GzmB was released from migrating cytotoxic lymphocytes and enabled chemokine-driven movement through basement membranes. Finally, proteomic analysis demonstrated that GzmB cleaved basement membrane constituents. Our results highlight an important role for GzmB in expediting cytotoxic lymphocyte diapedesis via basement membrane remodeling.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Killer Cells, Natural
/
T-Lymphocytes, Cytotoxic
/
Ectromelia, Infectious
/
Ectromelia virus
/
Granzymes
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Immunity
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2014
Type:
Article
Affiliation country:
Australia