Comparative study of in vitro inhibition of activation of the classical and alternative pathways of human complement by the magnesium and sodium salts of the anti-inflammatory peptide N-acetyl-aspartyl-glutamic acid (NAAGA).
The inhibitory activity of the sodium salt of the anti-inflammatory peptide N-acetyl-aspartyl-glutamic acid (NAAGA) on activation of the classical and alternative pathways of human complement was compared with that of the clinically used magnesium salt of NAAGA (NAAGA-Mg). Sodium salt of NAAGA (NAAGA-Na) inhibited both pathways of activation in a dose-dependent manner at concentration ranging from 1 to 10 mM by acting on formation and/or function of the C3 convertases as shown by the inhibitory capacity of the peptide on the release of the C3 cleavage fragment C3b and C3a. NAAGA-Na was as effective as NAAGA-Mg in inhibiting classical pathway activation at concentration above 10 mM. NAAGA-Na was more effective than NAAGA-Mg in inhibiting the alternative pathway since the sodium salt did not interfere with Mg-dependent formation of the alternative pathway C3 convertase.
Feuillard
J
J
INSERM U 28, Hôpital Broussais, Paris, France.
Maillet
F
F
Goldschmidt
P
P
Weiss
L
L
Kazatchkine
M D
MD
D000818:Animals; D003176:Complement C3 / Q000378:metabolism; D050577:Complement C3-C5 Convertases / Q000037:antagonists & inhibitors; D003169:Complement Inactivator Proteins / Q000494:pharmacology*; D003170:Complement Pathway, Alternative / Q000187:drug effects*; D003171:Complement Pathway, Classical / Q000187:drug effects*; D004151:Dipeptides / Q000494:pharmacology*; D006461:Hemolysis; D006801:Humans; D011817:Rabbits; D012756:Sheep
D003176:Complement C3; D003169:Complement Inactivator Proteins; D004151:Dipeptides; C027172:isospaglumic acid; D050577:Complement C3-C5 Convertases