Functional assessment of rat complement pathway activities and quantification of soluble C5b-9 in an experimental model of renal ischemia/reperfusion injury

J Immunol Methods. 2014 Oct:412:14-23. doi: 10.1016/j.jim.2014.06.011. Epub 2014 Jun 19.

Abstract

There is a growing interest in the monitoring of complement activation, not only in clinical settings but also in experimental models. However, for rodents only a limited number of tools are available to assess complement activity and activation. Here we describe three ELISAs for the measurement of rat classical (CP), MB-lectin (LP) and alternative (AP) pathway activities in serum and plasma. Moreover, we optimised a soluble C5b-9 (sC5b-9) ELISA for the detection of low level complement activation in rat. We determined the conditions for correct sample handling and showed that the assays had low inter- and intra-assay variation. We applied these assays to monitor complement activation in an experimental rat model of renal ischemia/reperfusion injury. We did not observe major complement consumption following reperfusion in CP or LP, and only minor AP consumption at 24h post reperfusion. However, MBL depletion prior to ischemia/reperfusion using a monoclonal antibody, transiently and specifically inhibited 75% of LP activity and ameliorated the AP consumption at 24h. To further assess complement activation during renal IRI, we monitored serum sC5b-9 and found that it was only significantly increased 72h post-reperfusion, but not when rats were pre-treated with anti-MBL or after sham surgery. In conclusion the described assays enable sensitive, reproducible and comprehensive assessment of complement activation in experimental rat models.

Keywords: Complement pathway activity; Functional complement activity ELISA; MBL; Renal ischemia/reperfusion injury; sC5b-9.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Blocking / administration & dosage
  • Complement Membrane Attack Complex / metabolism*
  • Complement Pathway, Alternative / immunology*
  • Complement Pathway, Classical / immunology*
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay / methods*
  • Female
  • Humans
  • Kidney / blood supply*
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Mannose-Binding Lectin / antagonists & inhibitors
  • Mannose-Binding Lectin / immunology*
  • Observer Variation
  • Rats
  • Rats, Inbred Lew
  • Rats, Wistar
  • Reperfusion Injury / immunology*

Substances

  • Antibodies, Blocking
  • Complement Membrane Attack Complex
  • Mannose-Binding Lectin