Document Detail


Effect of an anti-C5a monoclonal antibody indicates a prominent role for anaphylatoxin in pulmonary xenograft dysfunction.
MedLine Citation:
PMID:  16794535     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: In contrast to renal or cardiac xenografts, the inhibition of complement using cobra venom factor (CVF) accelerates pulmonary xenograft failure. By activating C3/C5 convertase, CVF depletes complement while additionally generating C5a and other anaphylatoxins, to which pulmonary xenografts may be uniquely susceptible. The current study investigates the role of C5a in pulmonary xenograft failure in baboons. METHODS: Left orthotopic pulmonary xenografts using swine lungs expressing human CD46 were performed in baboons receiving: I) no other treatment (n=4), II) immunodepletion (n=5), and III) immunodepletion plus a single dose of mouse anti-human C5a monoclonal antibody (anti-C5a, 0.6 mg/kg administered intravenously) (n=3). The extent to which anti-C5a inhibits baboon C5a was assessed in vitro using a hemolytic reaction involving baboon serum and porcine red blood cells and by ELISA. RESULTS: Baboons in Group III exhibited significantly prolonged xenograft survival (mean=722+/-121 min, P=0.02) compared to baboons in Group I (mean=202+/-24 min) and Group II (mean=276+/-79 min). Furthermore, baboons in Groups I and II experienced pronounced hemodynamic compromise requiring inotropic support whereas those in Group III remained hemodynamically stable throughout experimentation without the need for additional pharmacologic intervention. CONCLUSIONS: These findings indicate that C5a exacerbates pulmonary xenograft injury and compromises recipient hemodynamic status. Moreover, blockade of anaphylatoxins, such as C5a, offers a promising approach for future investigations aimed at preventing pulmonary xenograft injury in baboons.
Authors:
Jeffrey G Gaca; James Z Appel; Jeffrey G Lukes; Gonzalo V Gonzalez-Stawinski; Aaron Lesher; Daniel Palestrant; John S Logan; Stephanie D Love; Zoie E Holzknecht; Jeffrey L Platt; William Parker; R Duane Davis
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Transplantation     Volume:  81     ISSN:  0041-1337     ISO Abbreviation:  Transplantation     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-06-23     Completed Date:  2006-07-21     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1686-94     Citation Subset:  IM    
Affiliation:
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / immunology*,  pharmacology*
Blood Coagulation
Blood Pressure
Complement C5a / antagonists & inhibitors*,  immunology*
Endothelium / blood supply,  immunology,  pathology
Graft Rejection / immunology*,  metabolism,  pathology*,  physiopathology
Graft Survival
Humans
Immunohistochemistry
Lung Transplantation*
Papio
Swine
Transplantation, Heterologous
Grant Support
ID/Acronym/Agency:
HL 52297/HL/NHLBI NIH HHS; R01 HL 60232-03/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 80295-54-1/Complement C5a

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


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