Unknown

Dataset Information

0

The receptor for complement component C3a mediates protection from intestinal ischemia-reperfusion injuries by inhibiting neutrophil mobilization.


ABSTRACT: C3a is a key complement activation fragment, yet its neutrophil-expressed receptor (C3aR) still has no clearly defined role. In this study, we used a neutrophil-dependent mouse model of intestinal ischemia-reperfusion (IR) injury to explore the role of C3aR in acute tissue injuries. C3aR deficiency worsened intestinal injury, which corresponded with increased numbers of tissue-infiltrating neutrophils. Circulating neutrophils were significantly increased in C3aR(-/-) mice after intestinal ischemia, and C3aR(-/-) mice also mobilized more circulating neutrophils after granulocyte colony-stimulating factor infusion compared with WT mice, indicating a specific role for C3aR in constraining neutrophil mobilization in response to intestinal injury. In support of this role, C3aR(-/-) mice reconstituted with WT bone marrow reversed IR pathology back to WT levels. Complement C5a receptor (C5aR) antagonism in C3aR(-/-) mice also rectified the worsened pathology after intestinal IR injury but had no effect on circulating neutrophils, highlighting the opposing roles of C3a and C5a in disease pathogenesis. Finally, we found that using a potent C3a agonist to activate C3aR in vivo reduced neutrophil mobilization and ameliorated intestinal IR pathology in WT, but not C3aR(-/-), mice. This study identifies a role for C3aR in regulating neutrophil mobilization after acute intestinal injury and highlights C3aR agonism as a potential treatment option for acute, neutrophil-driven pathologies.

SUBMITTER: Wu MC 

PROVIDER: S-EPMC3677481 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

The receptor for complement component C3a mediates protection from intestinal ischemia-reperfusion injuries by inhibiting neutrophil mobilization.

Wu Mike C L MC   Brennan Faith H FH   Lynch Jason P L JP   Mantovani Susanna S   Phipps Simon S   Wetsel Rick A RA   Ruitenberg Marc J MJ   Taylor Stephen M SM   Woodruff Trent M TM  

Proceedings of the National Academy of Sciences of the United States of America 20130521 23


C3a is a key complement activation fragment, yet its neutrophil-expressed receptor (C3aR) still has no clearly defined role. In this study, we used a neutrophil-dependent mouse model of intestinal ischemia-reperfusion (IR) injury to explore the role of C3aR in acute tissue injuries. C3aR deficiency worsened intestinal injury, which corresponded with increased numbers of tissue-infiltrating neutrophils. Circulating neutrophils were significantly increased in C3aR(-/-) mice after intestinal ischem  ...[more]

Similar Datasets

| S-EPMC9529185 | biostudies-literature
| S-EPMC4552587 | biostudies-literature
| S-EPMC7993837 | biostudies-literature
| S-EPMC10967377 | biostudies-literature
| S-EPMC8744548 | biostudies-literature
| S-EPMC5156406 | biostudies-literature
| S-EPMC5056696 | biostudies-literature
| S-EPMC3736708 | biostudies-literature
| S-EPMC8047102 | biostudies-literature
| S-EPMC10313896 | biostudies-literature