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A soluble chimeric complement inhibitory protein that possesses both decay-accelerating and factor I cofactor activities.

P J Higgins, J L Ko, R Lobell, C Sardonini, M K Alessi and C G Yeh
J Immunol March 15, 1997, 158 (6) 2872-2881;
P J Higgins
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J L Ko
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R Lobell
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C Sardonini
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M K Alessi
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C G Yeh
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Abstract

A chimeric gene was constructed from the genes coding for the human complement regulatory proteins, membrane cofactor protein (CD46) and decay-accelerating factor (CD55). The recombinant chimeric gene was transfected into Chinese hamster ovary cells. The gene product is a soluble, glycosylated, 110-kDa protein named complement activation blocker-2 (CAB-2). This protein possesses both factor I cofactor activity and decay-accelerating activity, and inactivates classical and alternative C3/C5 convertases in vitro. The specific activity of CAB-2 against cell-associated convertases is greater than that of soluble forms of either membrane cofactor protein or decay-accelerating factor or of both factors combined. CAB-2 also blocks the activation of complement in vivo, inhibiting both the Arthus reaction and Forssman shock in guinea pigs. Studies in rats demonstrate CAB-2 to exhibit favorable biphasic pharmacokinetics with a t1/2 alpha of 10 min and a t1/2 beta of 8 h; the beta phase accounts for 93% of the administered dose. CAB-2 may be an effective therapeutic treatment of acute human diseases in which excessive complement activation causes damage to normal tissues.

  • Copyright © 1997 by American Association of Immunologists

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The Journal of Immunology
Vol. 158, Issue 6
15 Mar 1997
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A soluble chimeric complement inhibitory protein that possesses both decay-accelerating and factor I cofactor activities.
P J Higgins, J L Ko, R Lobell, C Sardonini, M K Alessi, C G Yeh
The Journal of Immunology March 15, 1997, 158 (6) 2872-2881;

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A soluble chimeric complement inhibitory protein that possesses both decay-accelerating and factor I cofactor activities.
P J Higgins, J L Ko, R Lobell, C Sardonini, M K Alessi, C G Yeh
The Journal of Immunology March 15, 1997, 158 (6) 2872-2881;
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Print ISSN 0022-1767        Online ISSN 1550-6606