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


Autoria(s): Gavins, FNE; Kamal, A. M.; D'Amico, M.; Oliani, S. M.; Perretti, M.
Contribuinte(s)

Universidade Estadual Paulista (UNESP)

Data(s)

20/05/2014

20/05/2014

01/10/2004

Resumo

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 (similar to9 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 A(4) 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.

Formato

100-+

Identificador

http://dx.doi.org/10.1096/fj.04-2178fje

Faseb Journal. Bethesda: Federation Amer Soc Exp Biol, v. 18, n. 13, p. 100-+, 2004.

0892-6638

http://hdl.handle.net/11449/21352

10.1096/fj.04-2178fje

WOS:000224849900007

Idioma(s)

eng

Publicador

Federation Amer Soc Exp Biol

Relação

FASEB Journal

Direitos

closedAccess

Palavras-Chave #FPR #ischemia/reperfusion #PMN
Tipo

info:eu-repo/semantics/article