Document Detail


The effect of bursectomy on natural xenoreactive antibodies and vascularized rat cardiac xenograft rejection in the chicken.
MedLine Citation:
PMID:  8497895     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The clinical application of xenotransplantation between distantly related species is currently prevented by the occurrence of hyperacute rejection (HAR). Controversy exists over the importance of natural xenoreactive antibody (NAb)-mediated activation of the classical complement pathway vs. direct activation of the alternative C pathway in this process. In order to evaluate HAR of xenografts (Xgs) in the absence of NAb, this study utilized K strain leghorn chickens that were bursectomized (Bx) on day 17 in ovo (n = 18) to prevent B cell development and production of NAb. Aged-matched untreated siblings served as controls (n = 13). Based on pretransplant antibody levels, the Bx chickens were divided into two groups: totally Bx (Total Bx, n = 9) and partially Bx (Part Bx, n = 9). Chickens then underwent heterotopic cardiac xenotransplantation using PVG rats as donors, where the Xg was connected to the circulation of the chicken recipient utilizing cannulae. For the control group, Xg survival was 28 +/- 3 min (mean +/- SEM), while Part Bx prolonged survival to 80 +/- 15 min. Total Bx extended rat Xg survival to 102 +/- 11 min, with 5 of 9 Xgs functioning well at the time of termination of the study (90-120 min). Three chickens in the Total Bx group with rat cardiac Xgs that were functioning at 120 min were given a 1 ml i.v. injection of heat inactivated control chicken serum. This led to loss of Xg function within 10 min, confirming the important role for NAb in HAR in this species combination. Histologic examination of the Xgs following perfusion revealed significant arterial endothelial injury in the control and Part Bx groups but not in the Total Bx group. Conversely, Xgs from the Total Bx group showed marked venous congestion, which was not seen in the other two groups. This study demonstrates that: (1) Bx effectively eliminates NAb; (2) Xg survival is significantly prolonged in the absence of NAb in this rat-to-chicken xenogeneic combination; (3) the presence of NAb is associated with arterial endothelial injury; and (4) in the absence of NAb, marked venous congestion and injury occurs, which is possibly mediated by alternative C pathway activation or other humoral mechanisms.
Authors:
S K Pruitt; D Weinstock; M M Suyemoto; F Sanfilippo; W M Baldwin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Transplantation     Volume:  55     ISSN:  0041-1337     ISO Abbreviation:  Transplantation     Publication Date:  1993 May 
Date Detail:
Created Date:  1993-06-21     Completed Date:  1993-06-21     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1139-44     Citation Subset:  IM    
Affiliation:
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies / immunology*,  metabolism
Binding Sites, Antibody
Bursa of Fabricius / surgery*
Chickens
Complement Pathway, Alternative
Complement Pathway, Classical
Graft Rejection
Graft Survival
Heart Transplantation / immunology*
Immunization, Passive
Immunoglobulin G / blood
Immunoglobulin M / blood
Rats
Transplantation, Heterologous* / pathology,  physiology
Grant Support
ID/Acronym/Agency:
P01 AI19368/AI/NIAID NIH HHS; T32 HL07671/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies; 0/Binding Sites, Antibody; 0/Immunoglobulin G; 0/Immunoglobulin M

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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