Document Detail

Use of C6-deficient rats to evaluate the mechanism of hyperacute rejection of discordant cardiac xenografts.
MedLine Citation:
PMID:  8258722     Owner:  NLM     Status:  MEDLINE    
C plays a critical role in the hyperacute rejection (HAR) of discordant xenografts (Xg), but the relative contribution of early vs late C components is unknown. In this study, genetic differences in C6 activity were correlated with HAR of guinea pig cardiac Xg by the rat. Seven rat strains were tested for C activity. Six strains (PVG.R1 (R1), PVG.1A (1A), DA, W/F, F344, LEW) had readily detectable C activity in the total and alternative pathways. Some PVG rats also had adequate C activity [PVG (C+)] but others [PVG (C-)] had a profound C6 deficiency. All rats with adequate C activity (n = 35) rejected cardiac Xg between 15 and 80 min. PVG (C+) (n = 6) rats also rejected cardiac Xg hyperacutely (26 +/- 12 min), whereas PVG (C-) (n = 16) rats, which had high preformed IgM natural antibody titers, rejected cardiac Xg in 1 to 2 days (2678 +/- 542 min). Transfer of serum from R1 rats to PVG (C-) recipients with vigorously beating Xg caused HAR of cardiac Xg within 116 +/- 75 min. Transfer of fresh PVG (C-) serum or heat-inactivated R1 serum did not induce HAR. HAR was characterized by intravascular platelet aggregation and interstitial hemorrhage, whereas Xg transplanted to PVG (C-) recipients had patent vessels at 30 min but were heavily infiltrated by granulocytes and monocytes at 2 days. These findings indicate that a deficiency in C6 prevents HAR but allows an accelerated acute rejection that may be mediated by the generation of vasoactive and chemotactic C3a and C5a.
R B Brauer; W M Baldwin; M R Daha; S K Pruitt; F Sanfilippo
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  151     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  1993 Dec 
Date Detail:
Created Date:  1994-01-14     Completed Date:  1994-01-14     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  7240-8     Citation Subset:  AIM; IM    
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
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MeSH Terms
Complement C3 / metabolism
Complement C5 / metabolism
Complement C6 / deficiency*,  genetics
Complement Hemolytic Activity Assay
Complement Pathway, Alternative
Graft Rejection*
Heart Transplantation / adverse effects,  immunology*,  pathology
Immunoglobulin M / metabolism
Myocardium / immunology,  pathology
Rats, Inbred Strains
Transplantation, Heterologous
Grant Support
Reg. No./Substance:
0/Complement C3; 0/Complement C5; 0/Complement C6; 0/Immunoglobulin M

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