Protection from complement-mediated injury in livers and kidneys of transgenic mice expressing human complement regulators

Marirosa Mora, Lubbertus C F Mulder, Massimo Lazzeri, Manuela Boschi, Eugenia Ciccopiedi, Cristina M. Melli, Paolo Bruzzone, Dario Alfani, Raffaello Cortesini, Mara Rossini

Research output: Contribution to journalArticle

Abstract

The major problem in the use of phylogenetically distant donors is a fast, strong reaction called hyperacute rejection. This reaction mediated by complement is directed against the vascular endothelia of the transplanted organ. Complement activation is tightly controlled by several regulatory proteins which inhibit the formation and function of different complement components. To verify the hypothesis that organs expressing such inhibitory factors could be spared from complement-mediated hyperacute rejection, we have generated mice transgenic for the human complement inhibitor membrane cofactor protein (hMCP) and decay accelerating factor (hDAF). Different levels of hMCP and/or hDAF expression, according to the promoter used, were detected by RNA analysis in the major organs, specifically on the organ vascular endothelia, as revealed by immunohistochemical analysis. The development of an in vivo model of human plasma perfusion allowed the characterization of complement-mediated damage in control animals and the degree of protection due to the presence of hMCP, hDAF, or both in the organs derived from single or double transgenic mice. In this paper we compare the level of expression of complement regulators with the degree of protection in two major organs: liver and kidney.

Original languageEnglish
Pages (from-to)63-68
Number of pages6
JournalXenotransplantation
Volume3
Issue number1 PART 2
Publication statusPublished - 1996

Fingerprint

Complement Inactivating Agents
CD46 Antigens
CD55 Antigens
Transgenic Mice
Kidney
Liver
Vascular Endothelium
Wounds and Injuries
Complement Activation
Perfusion
RNA
Proteins

Keywords

  • Human complement regulators
  • Hyperacute rejection
  • In vivo perfusion with human plasma
  • MCP-DAF transgenic mice

ASJC Scopus subject areas

  • Immunology

Cite this

Mora, M., Mulder, L. C. F., Lazzeri, M., Boschi, M., Ciccopiedi, E., Melli, C. M., ... Rossini, M. (1996). Protection from complement-mediated injury in livers and kidneys of transgenic mice expressing human complement regulators. Xenotransplantation, 3(1 PART 2), 63-68.

Protection from complement-mediated injury in livers and kidneys of transgenic mice expressing human complement regulators. / Mora, Marirosa; Mulder, Lubbertus C F; Lazzeri, Massimo; Boschi, Manuela; Ciccopiedi, Eugenia; Melli, Cristina M.; Bruzzone, Paolo; Alfani, Dario; Cortesini, Raffaello; Rossini, Mara.

In: Xenotransplantation, Vol. 3, No. 1 PART 2, 1996, p. 63-68.

Research output: Contribution to journalArticle

Mora, M, Mulder, LCF, Lazzeri, M, Boschi, M, Ciccopiedi, E, Melli, CM, Bruzzone, P, Alfani, D, Cortesini, R & Rossini, M 1996, 'Protection from complement-mediated injury in livers and kidneys of transgenic mice expressing human complement regulators', Xenotransplantation, vol. 3, no. 1 PART 2, pp. 63-68.
Mora, Marirosa ; Mulder, Lubbertus C F ; Lazzeri, Massimo ; Boschi, Manuela ; Ciccopiedi, Eugenia ; Melli, Cristina M. ; Bruzzone, Paolo ; Alfani, Dario ; Cortesini, Raffaello ; Rossini, Mara. / Protection from complement-mediated injury in livers and kidneys of transgenic mice expressing human complement regulators. In: Xenotransplantation. 1996 ; Vol. 3, No. 1 PART 2. pp. 63-68.
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