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

: 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...

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Published in:Xenotransplantation (Københaven) 2003-05, Vol.10 (3), p.267-277
Main Authors: Malassagne, B., Regimbeau, J. M., Taboit, F., Troalen, F., Chéreau, C., Moiré, N., Attal, J., Batteux, F., Conti, F., Calmus, Y., Houssin, D., Boulard, C., Houdebine, L. M., Weill, B.
Format: Article
Language:English
Subjects:
Acute Disease
Amino Acid Sequence
Animals
Cell Survival
CHO Cells
complement
Complement C3 - metabolism
Complement C6 - metabolism
Complement Inactivator Proteins - pharmacology
Complement Membrane Attack Complex - metabolism
Cricetinae
endothelial cells
Endothelium, Vascular - cytology
Graft Rejection - prevention & control
Graft Survival - immunology
Heart Transplantation - immunology
Humans
hypodermin A
Life Sciences
molecular biology
Molecular Sequence Data
Rats
Serine Endopeptidases - chemistry
Serine Endopeptidases - isolation & purification
Serine Endopeptidases - pharmacology
Swine
Transfection
Transplantation, Heterologous - immunology
xenotransplantation
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Summary:: 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 
ISSN:0908-665X
1399-3089
DOI:10.1034/j.1399-3089.2003.02030.x