Cross-species function of the pig C1 esterase inhibitor.
BACKGROUND
The use of a bioartificial liver with pig cells for the treatment of fulminant hepatic failure will require research on the plasma complement regulatory proteins of the pig, because the liver produces most of the complement components and plasma complement regulatory proteins. In our previous study, the pig C1 esterase inhibitor (C1-INH), which functions as an inhibitor of the complement reaction in the first step of the classical pathway in the fluid phase, was cloned and some relevant features of the molecule were characterized, especially its cross-species regulation, in comparison with human C1-INH. In a further analysis, the species specificity of C1-INH was examined, using pig endothelial cells (PEC) and several types of sera.


METHODS
The cDNA of pig C1-INH was used to produce the membrane type pC1-INH, pC1-INH-PI, and inserted into the cloning site of pCXN2 (chicken beta actin promoter). The pCX/pCl-INH-PI plasmid was then transfected into PEC to establish stable PEC with pCl-INH-PI. The expression of the pCl-INH-PI was evaluated by a FACS analysis, and complement-dependent cell lysis with human, dog, rabbit, and mouse sera was then assessed.


RESULTS
The transfectant with pig Cl-INH-PI showed a high level of expression on PEC. The PEC transfectants showed an inhibitory effect on complement-dependent PEC lysis. Pig Cl-INH did not show the same suppressive effect for each serum. However, considering the alternative pathway activation of each serum on the pig cell membrane, it can be concluded that pCl-INH has a relatively small species restriction.


CONCLUSIONS
Pig Cl-INH, having a similar structure to human Cl-INH, shows a strong complement regulatory function on other species sera.
Koboyashi
C
C
Department of Organ Transplantation, Osaka University Graduate School of Medicine, Osaka, Japan.
Matsunami
K
K
Omori
T
T
Nakahata
K
K
Nakatsu
S
S
Xu
H
H
Gao
C
C
Ihara
Y
Y
Fukuzawa
M
M
Miyagawa
S
S
D000199:Actins / Q000235:genetics; D000818:Animals; D002645:Chickens; D003174:Complement C1 Inactivator Proteins / Q000235:genetics / Q000502:physiology*; D019164:Liver, Artificial; D011401:Promoter Regions, Genetic; D013045:Species Specificity; D013552:Swine; D014162:Transfection
D000199:Actins; D003174:Complement C1 Inactivator Proteins