Hypodermin A, a new inhibitor of human complement for the prevention of xenogeneic hyperacute rejection

Autor: Frédérique Taboit, N. Moiré, F. Troalen, Bernard Weill, Louis-Marie Houdebine, Didier Houssin, J. M. Regimbeau, Christiane Chéreau, Joe Attal, Benoît Malassagne, Filomena Conti, Frédéric Batteux, Yvon Calmus, C. Boulard
Rok vydání: 2003
Předmět:
Zdroj: Xenotransplantation. 10:267-277
ISSN: 0908-665X
Popis: Background: Hyperacute rejection (HAR) of discordant xenografts in the pig-to-human combination can be prevented using tranplants expressing transgenic molecules that inhibit human complement. Hypodermin A (HA), a serine esterase that degrades C3, was tested in the guinea-pig-to-rat and in the pig-to-human combinations. Methods: Hypodermin A was tested in vitro, ex vivo, and in vivo models of HAR in the guinea-pig-to-rat combination. Hamster ovary cells (CHO) and a line of porcine aortic endothelial cells (PAEC11) were transfected with HA complementary DNA (cDNA). Results: The pattern of degradation of rat and human C3 by HA was different (multiple bands lower than 40 kDa) from the physiologic pattern observed after spontaneous degradation of rat C3 or physiologic activation of human C3. The CH50 activity in serum was significantly lower in rats treated with 3.2 mg HA/kg than in untreated rats (45 ± 16 U/ml vs. 700 ± 63 U/ml, P
Databáze: OpenAIRE