Sterile inflammation of endothelial cell-derived apoptotic bodies is mediated by interleukin-1α.
Proc Natl Acad Sci U S A
; 108(51): 20684-9, 2011 Dec 20.
Article
in En
| MEDLINE
| ID: mdl-22143786
Sterile inflammation resulting from cell death is due to the release of cell contents normally inactive and sequestered within the cell; fragments of cell membranes from dying cells also contribute to sterile inflammation. Endothelial cells undergoing stress-induced apoptosis release membrane microparticles, which become vehicles for proinflammatory signals. Here, we show that stress-activated endothelial cells release two distinct populations of particles: One population consists of membrane microparticles (<1 µm, annexin V positive without DNA and no histones) and another larger (1-3 µm) apoptotic body-like particles containing nuclear fragments and histones, representing apoptotic bodies. Contrary to present concepts, endothelial microparticles do not contain IL-1α and do not induce neutrophilic chemokines in vitro. In contrast, the large apoptotic bodies contain the full-length IL-1α precursor and the processed mature form. In vitro, these apoptotic bodies induce monocyte chemotactic protein-1 and IL-8 chemokine secretion in an IL-1α-dependent but IL-1ß-independent fashion. Injection of these apoptotic bodies into the peritoneal cavity of mice induces elevated serum neutrophil-inducing chemokines, which was prevented by cotreatment with the IL-1 receptor antagonist. Consistently, injection of these large apoptotic bodies into the peritoneal cavity induced a neutrophilic infiltration that was prevented by IL-1 blockade. Although apoptosis is ordinarily considered noninflammatory, these data demonstrate that nonphagocytosed endothelial apoptotic bodies are inflammatory, providing a vehicle for IL-1α and, therefore, constitute a unique mechanism for sterile inflammation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Endothelial Cells
/
Interleukin-1alpha
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2011
Document type:
Article