Functional activity of anti-C6 antibodies elicited in C6-deficient rats reconstituted by liver allografts

Ability to inhibit hyperacute rejection of discordant cardiac xenografts

Robert B. Brauer, William M. Baldwin, Dajie Wang, Scott K. Pruitt, Andrew S. Klein, Fred Sanfilippo

Research output: Contribution to journalArticle

Abstract

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-) (RT1(c)) rats that reject guinea pig cardiac xenografts at a delayed tempo (45±9 hr; n=16) compared with C6-sufficient PVG (C+) (RT1(c)) 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 (RT11) 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

Original languageEnglish (US)
Pages (from-to)588-594
Number of pages7
JournalTransplantation
Volume61
Issue number4
DOIs
StatePublished - Feb 27 1996

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Heterografts
Allografts
Anti-Idiotypic Antibodies
Liver
Guinea Pigs
Complement Membrane Attack Complex
Immune Sera
Antibodies
Complement C6
Transplants
Reperfusion
Complement System Proteins
Immunoglobulin G

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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Functional activity of anti-C6 antibodies elicited in C6-deficient rats reconstituted by liver allografts : Ability to inhibit hyperacute rejection of discordant cardiac xenografts. / Brauer, Robert B.; Baldwin, William M.; Wang, Dajie; Pruitt, Scott K.; Klein, Andrew S.; Sanfilippo, Fred.

In: Transplantation, Vol. 61, No. 4, 27.02.1996, p. 588-594.

Research output: Contribution to journalArticle

Brauer, Robert B. ; Baldwin, William M. ; Wang, Dajie ; Pruitt, Scott K. ; Klein, Andrew S. ; Sanfilippo, Fred. / Functional activity of anti-C6 antibodies elicited in C6-deficient rats reconstituted by liver allografts : Ability to inhibit hyperacute rejection of discordant cardiac xenografts. In: Transplantation. 1996 ; Vol. 61, No. 4. pp. 588-594.
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abstract = "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-) (RT1(c)) rats that reject guinea pig cardiac xenografts at a delayed tempo (45±9 hr; n=16) compared with C6-sufficient PVG (C+) (RT1(c)) 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 (RT11) 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",
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