Document Detail

Functional activity of anti-C6 antibodies elicited in C6-deficient rats reconstituted by liver allografts. Ability to inhibit hyperacute rejection of discordant cardiac xenografts.
MedLine Citation:
PMID:  8610386     Owner:  NLM     Status:  MEDLINE    
A critical role of the complement membrane attack complex (C5b-9) in mediating hyperacute rejection has been demonstrated previously in fully C6-deficient PVG (C-)(RT1c) rats that reject guinea pig cardiac xenografts at a delayed tempo (45 +/- 9 hr; n=16) compared with C6-sufficient PVG (C+)(RT1c) hosts (0.5 +/- 2 hr; n=6). We have investigated whether selective depletion of C6 from Lewis rats by antibody therapy prevents hyperacute rejection. A polyclonal rat-antirat C6 antibody was induced in PVG (C-) recipients by orthotopic liver transplants from congenic PVG (C+) donors. These liver grafts produced high levels of C6 that reconstituted the complement function of PVG (C-) hosts by 7 days, but the recipients responded within 28 days with the synthesis of an IgG1 antibody to rat C6. The antiserum inhibited hemolytic complement activity of Lewis (RT1(1)) rats in vivo and in vitro. The effect of C6 depletion on Xg survival was investigated by injecting Lewis rats with 2 ml of rat-antirat C6 antiserum before and 1 ml after reperfusion of the guinea pig cardiac xenograft. Lewis rats rejected guinea pig cardiac xenografts after treatment with this rat-antirat C6 antiserum in 38 +/ -11 hr (n=3). Treatment with normal control sera from PVG (C-) rats did not prolong guinea pig cardiac xenograft survival in the Lewis rats (1 +/- 0.7 hr; n=3)(P<0.0043). Injection of 3 ml of the IgG fraction purified from the rat-antirat C6 antibody (33 mg/ml) prolonged xenograft survival to 13.6 +/- 4 hr (n=4) compared with the survival of 0.61 +/- 0.3 hr (n=4) after injection of control rat IgG (33 mg/ml) (P<0.005). These results demonstrate that specific depletion of C6 by antibody therapy has a significant effect on guinea pig cardiac xenograft survival in the Lewis rat. These findings further suggest that C6 depletion may be beneficial to patients undergoing hyperacute rejection of xenografts or allografts.
R B Brauer; W M Baldwin; D Wang; S K Pruitt; A S Klein; F Sanfilippo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Transplantation     Volume:  61     ISSN:  0041-1337     ISO Abbreviation:  Transplantation     Publication Date:  1996 Feb 
Date Detail:
Created Date:  1996-05-24     Completed Date:  1996-05-24     Revised Date:  2010-04-08    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  588-94     Citation Subset:  IM    
Department of Pathology and Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland, 21205-2191, USA.
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MeSH Terms
Antibodies / blood,  pharmacology,  physiology*
Antibodies, Monoclonal / pharmacology
Antibody Formation
Blotting, Western
Complement C6 / deficiency*,  immunology
Complement Hemolytic Activity Assay
Graft Survival / immunology
Guinea Pigs
Heart Transplantation
Liver Transplantation / immunology*
Rats, Inbred Lew
Transplantation, Heterologous
Reg. No./Substance:
0/Antibodies; 0/Antibodies, Monoclonal; 0/Complement C6

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