Monomeric C-reactive protein inhibits renal cell-directed complement activation mediated by properdin

Joseph O’Flynn, Pieter van der Pol, Karen O. Dixon, Z. Prohászka, Mohamed R. Daha, Cees van Kooten

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Previous studies have shown that complement activation on renal tubular cells is involved in the induction of interstitial fibrosis and cellular injury. Evidence suggests that the tubular cell damage is initiated by the alternative pathway (AP) of complement with properdin having an instrumental role. Properdin is a positive regulator of the AP, which can bind necrotic cells as well as viable proximal tubular epithelial cells (PTECs), inducing complement activation. Various studies have indicated that in the circulation there is an unidentified inhibitor of properdin. We investigated the ability of C-reactive protein (CRP), both in its monomeric (mCRP) and pentameric (pCRP) form, to inhibit AP activation and injury in vitro on renal tubular cells by fluorescent microscopy, ELISA, and flow cytometry. We demonstrated that preincubation of properdin with normal human serum inhibits properdin binding to viable PTECs. We identified mCRP as a factor able to bind to properdin in solution, thereby inhibiting its binding to PTECs. In contrast, pCRP exhibited no such binding and inhibitory effect. Furthermore, mCRP was able to inhibit properdin-directed C3 and C5b-9 deposition on viable PTECs. The inhibitory ability of mCRP was not unique for viable cells but also demonstrated for binding to necrotic Jurkat cells, a target for properdin binding and complement activation. In summary, mCRP is an inhibitor of properdin in both binding to necrotic cells and viable renal cells, regulating complement activation on the cell surface. We propose that mCRP limits amplification of tissue injury by controlling properdin-directed complement activation by damaged tissue and cells.

Original languageEnglish
Pages (from-to)F1308-F1316
JournalAmerican Journal of Physiology - Renal Physiology
Volume310
Issue number11
DOIs
Publication statusPublished - Jun 1 2016

Fingerprint

Properdin
Complement Activation
C-Reactive Protein
Kidney
Epithelial Cells
Wounds and Injuries
Alternative Complement Pathway
Complement Membrane Attack Complex
Jurkat Cells
Microscopy
Flow Cytometry
Fibrosis
Enzyme-Linked Immunosorbent Assay

Keywords

  • Alternative pathway
  • C-reactive protein
  • Kidney
  • Properdin
  • Proximal tubular epithelial cell

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Monomeric C-reactive protein inhibits renal cell-directed complement activation mediated by properdin. / O’Flynn, Joseph; van der Pol, Pieter; Dixon, Karen O.; Prohászka, Z.; Daha, Mohamed R.; van Kooten, Cees.

In: American Journal of Physiology - Renal Physiology, Vol. 310, No. 11, 01.06.2016, p. F1308-F1316.

Research output: Contribution to journalArticle

O’Flynn, Joseph ; van der Pol, Pieter ; Dixon, Karen O. ; Prohászka, Z. ; Daha, Mohamed R. ; van Kooten, Cees. / Monomeric C-reactive protein inhibits renal cell-directed complement activation mediated by properdin. In: American Journal of Physiology - Renal Physiology. 2016 ; Vol. 310, No. 11. pp. F1308-F1316.
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