Human xenoreactive natural antibodies of the IgM isotype activate pig endothelial cells |
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Authors: | Bernard Vanhove Rainer de Martin Joachim Lipp Fritz H Bach |
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Institution: | Vienna International Research Cooperation Center (VIRCC), Vienna, Austria;and Sandoz Center for Immunobiology, Harvard Medical School, Boston, MA, U.S.A.;Sandoz Center for Immunobiology, Harvard Medical School, Boston, MA, U.S.A. |
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Abstract: | Abstract: Preformed, xenoreactive natural antibodies (XNA) and complement (C) are involved in the initiation of vascular rejection of organs transplanted between discordant species, presumably by stimulating donor organ endothelial cells (EC). Although C is known to play a role in the activation of EC, it has not been clear whether the antibodies serve only to anchor the initial components of C, and thus permit the C cascade to proceed, or whether the antibodies themselves deliver a signal to the EC. We have tested affinity-purified human IgM containing XNA (IgM-XNA) for its ability to stimulate in vitro the up-regulation of genes in pig EC. Northern blot analysis shows that IgM, which contains XNA, stimulates mRNA accumulation for certain genes (including IL-8, PAI-1, and ECI-7, a new gene that we have found is associated with EC activation), but not others known to be up-regulated in response to TNF, IL-1 or LPS. Our results show that XNA provide a signal to EC, and thus may themselves participate in activation of EC and consequent vascular rejection. |
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Keywords: | endothelial cell xenoreactivity natural antibodies |
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