Assuntos
Fármacos Cardiovasculares/uso terapêutico , Endotoxinas/toxicidade , Proteínas de Choque Térmico HSP70/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Choque/tratamento farmacológico , Animais , Pressão Sanguínea/efeitos dos fármacos , Bovinos , Modelos Animais de Doenças , Escherichia coli , Proteínas de Choque Térmico HSP70/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Humanos , Lipopolissacarídeos/toxicidade , Masculino , Músculo Esquelético/metabolismo , Ratos , Ratos Sprague-Dawley , Choque/induzido quimicamente , Choque/mortalidade , Fatores de TempoRESUMO
We have synthesized two peptides, VKGFY and cyclo(VKGFY) (referred to as pentarphin (PNT) and cyclopentarphin (cPNT), respectively), and found that both peptides at 1 nM concentration increased the adhesion and spreading of murine peritoneal macrophages as well as their bactericidal activity in vitro, as shown by phagocytosis of Salmonella typhimurium virulent strain 415. PNT administered intraperitoneally at dose 20 microg/mouse on day 7, 3, and 1 prior to the isolation of macrophages also enhanced the macrophage adhesion and spreading. The receptor binding characteristics of PNT and cPNT were examined using 125I-labeled PNT. The binding of labeled PNT to peritoneal macrophages was high-affinity (K(d)=3.6 nM) and saturable. It was not inhibited by naloxone (NAL) or [Met(5)]enkephalin ([Met(5)]ENK) but completely inhibited by unlabeled cPNT (K(i)=2.6 nM), immunorphin (IMN, decapeptide SLTCLVKGFY, corresponding to the IgG heavy-chain sequence 364-373) (K(i)=3.2 nM) or beta-endorphin (beta-END) (K(i)=2.8 nM). Thus, the effects of PNT and cPNT on macrophages are mediated by NAL-insensitive receptors common for PNT, cPNT, IMN, and beta-END.