Formyl-peptide receptor is not involved in the protection afforded by annexin 1 in murine acute myocardial infarct.

Abstract

Recent interest in the annexin 1 field has come from the notion that specific G-protein-coupled receptors, members of the formyl-peptide receptor (FPR) family, appear to mediate the anti-inflammatory actions of this endogenous mediator. Administration of the annexin 1 N-terminal derived peptide Ac2-26 to mice after 25 min ischemia significantly attenuated the extent of acute myocardial injury as assessed 60 min postreperfusion. Evident at the dose of 1 mg/kg (approximately 9 nmol per animal), peptide Ac2-26 cardioprotection was intact in FPR null mice. Similarly, peptide Ac2-26 inhibition of specific markers of heart injury (specifically myeloperoxidase activity, CXC chemokine KC contents, and endogenous annexin 1 protein expression) was virtually identical in heart samples collected from wild-type and FPR null mice. Mouse myocardium expressed the mRNA for FPR and the structurally related lipoxin A4 receptor, termed ALX; thus, comparable equimolar doses of two ALX agonists (W peptide and a stable lipoxin A4 analog) exerted cardioprotection in wild-type and FPR null mice to an equal extent. Curiously, marked (>95%) blood neutropenia produced by an anti-mouse neutrophil serum did not modify the extent of acute heart injury, whereas it prevented the protection afforded by peptide Ac2-26. Thus, this study sheds light on the receptor mechanism(s) mediating annexin 1-induced cardioprotection and shows a pivotal role for ALX and circulating neutrophil, whereas it excludes any functional involvement of mouse FPR. These mechanistic data can help in developing novel therapeutics for acute cardioprotection.

• Authors: Felicity N E Gavins, Ahmad M Kamal, Michele D'Amico, Sonia M Oliani, Mauro Perretti
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 19 Issue 1 Pg. 100-2 (Jan 2005) ISSN: 1530-6860 [Electronic] United States
• PMID: 15507472 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Annexin A1
• Biomarkers
• Cardiotonic Agents
• Fpr1 protein, mouse
• Peptides
• Receptors, Formyl Peptide

Topics

• Amino Acid Sequence
• Animals
• Annexin A1 (physiology)
• Biomarkers
• Cardiotonic Agents (pharmacology)
• Inflammation (metabolism)
• Mice
• Mice, Inbred C57BL
• Molecular Mimicry
• Molecular Sequence Data
• Myocardial Infarction (prevention & control)
• Myocardial Reperfusion Injury
• Neutrophils (metabolism)
• Peptides (chemistry, pharmacology)
• Receptors, Formyl Peptide (deficiency, metabolism, physiology)