Inhibiting membrane rupture with NINJ1 antibodies limits tissue injury.
Nature
; 618(7967): 1072-1077, 2023 Jun.
Article
in En
| MEDLINE
| ID: mdl-37196676
ABSTRACT
Plasma membrane rupture (PMR) in dying cells undergoing pyroptosis or apoptosis requires the cell-surface protein NINJ11. PMR releases pro-inflammatory cytoplasmic molecules, collectively called damage-associated molecular patterns (DAMPs), that activate immune cells. Therefore, inhibiting NINJ1 and PMR may limit the inflammation that is associated with excessive cell death. Here we describe an anti-NINJ1 monoclonal antibody that specifically targets mouse NINJ1 and blocks oligomerization of NINJ1, preventing PMR. Electron microscopy studies showed that this antibody prevents NINJ1 from forming oligomeric filaments. In mice, inhibition of NINJ1 or Ninj1 deficiency ameliorated hepatocellular PMR induced with TNF plus D-galactosamine, concanavalin A, Jo2 anti-Fas agonist antibody or ischaemia-reperfusion injury. Accordingly, serum levels of lactate dehydrogenase, the liver enzymes alanine aminotransaminase and aspartate aminotransferase, and the DAMPs interleukin 18 and HMGB1 were reduced. Moreover, in the liver ischaemia-reperfusion injury model, there was an attendant reduction in neutrophil infiltration. These data indicate that NINJ1 mediates PMR and inflammation in diseases driven by aberrant hepatocellular death.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Reperfusion Injury
/
Cell Membrane
/
Inflammation
/
Liver
/
Antibodies, Monoclonal
/
Nerve Growth Factors
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Nature
Year:
2023
Document type:
Article
Affiliation country:
United States