Non-Complement- and Complement-Activating Antibodies Synergize to Cause Rejection of Cardiac Allografts

Salma Rahimi, Zhiping Qian, Jodi Layton, Karen Fox-Talbot, William M. Baldwin, Barbara A. Wasowska

Research output: Contribution to journalArticlepeer-review

Abstract

Alloantibodies (AlloAbs) are a clinically significant component of the immune response to organ transplants. In our experimental model, B10.A (H-2 a) cardiac transplants survived significantly longer in C57BL/6 (H-2b) immunoglobulin knock-out (IgKO) recipients than in their wild-type (WT) counterparts. Passive transfer of a single 50-200-μg dose of complement-activating IgG2b AlloAbs to IgKO recipients reconstituted acute rejection of cardiac allografts. Although passive transfer of a subthreshold dose of 25 μg of IgG2b or a single 100-200-μg dose of non-complement-activating IgG1 AlloAbs did not restore acute rejection to IgKO recipients, a combination of these AlloAbs did cause acute graft rejection. Histologically, rejection was accompanied by augmented release of von Willebrand factor from endothelial cells. IgG1 AlloAbs did not activate complement on their own and did not augment complement activation by IgG2b AlloAbs. However, IgG1 AlloAbs stimulated cultured mouse endothelial cells to produce monocyte chemotactic protein 1 (MCP-1) and neutrophil chemoattractant growth-related oncogene α (KC). TNF-α augmented IgG1 induced secretion of MCP-1 and KC. These findings indicate that non-complement-activating AlloAbs can augment injury to allografts by complement-activating AlloAbs. Non-complement-activating AlloAbs stimulate endothelial cells to produce chemokines and this effect is augmented in the milieu of proinflammatory cytokines.

Original languageEnglish (US)
Pages (from-to)326-334
Number of pages9
JournalAmerican Journal of Transplantation
Volume4
Issue number3
DOIs
StatePublished - Mar 2004

Keywords

  • Alloantibodies
  • Cardiac transplant
  • Complement
  • Cytokines
  • IgKO

ASJC Scopus subject areas

  • Immunology

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