Premium
Role of the mouse complement components C5 and C3a in a model of myocardial ischemia and reperfusion injury
Author(s) -
Busche Marc Nicolai,
Walsh Mary C,
Stahl Gregory L
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a12-a
Subject(s) - medicine , anaphylatoxin , neutropenia , ischemia , complement system , reperfusion injury , pharmacology , antagonist , troponin t , receptor , receptor antagonist , monoclonal antibody , cardiology , immunology , myocardial infarction , antibody , chemotherapy
Ischemic heart disease is the leading cause of death worldwide. Previous studies have shown that inhibition of C5 is protective in myocardial ischemia and reperfusion (MI/R) injury. However, the role of early complement components upstream from C5 cleavage (e.g., C3a) has not been elucidated. Therefore, we evaluated the role of C5 and C3a in a mouse model of MI/R injury. In wild type mice, MI/R (30 min I and 4 hours of R) induced a significant decrease in ejection fraction, an increase in serum troponin I levels and myocardial neutrophil infiltration. Systemic C5 inhibition with an anti‐C5 monoclonal antibody 30 min prior to R significantly protected mice from MI/R injury. These results confirm an important role for C5 in MI/R injury. Since the C3a receptor antagonist (C3aRA; Calbiochem) induces neutropenia that resolves within 120 min, we administered C3aRA at two different time points in two separate groups. Treatment 30 min prior to R (i.e., within the neutropenic timeframe) protected mice significantly from MI/R injury. Administration 120 min prior to R, when the neutropenia had resolved, but C3aRA was still active, did not prevent mice from MI/R associated injury. These results suggest a minimal role for C3a, since neutropenia rather than C3a receptor antagonism appears to be responsible for C3aRA related amelioration in MI/R injury. This project was supported by NIH HL56068, HL52886, HL79758 and DE017821.