C-reactive protein and pentraxin-3 binding of factor H-like protein 1 differs from complement factor H

Implications for retinal inflammation

Maurice Swinkels, Justine H. Zhang, Viranga Tilakaratna, Graeme Black, Rahat Perveen, Selina McHarg, Antonio Inforzato, Anthony J. Day, Simon J. Clark

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Retinal inflammation plays a key role in the progression of age-related macular degeneration (AMD), a condition that leads to loss of central vision. The deposition of the acute phase pentraxin C-reactive protein (CRP) in the macula activates the complement system, thereby contributing to dysregulated inflammation. The complement protein factor H (FH) can bind CRP and down-regulate an inflammatory response. However, it is not known whether a truncated form of FH, called factor H-like protein 1 (FHL-1), which plays a significant regulatory role in the eye, also interacts with CRP. Here, we compare the binding properties of FHL-1 and FH to both CRP and the related protein pentraxin-3 (PTX3). We find that, unlike FH, FHL-1 can bind pro-inflammatory monomeric CRP (mCRP) as well as the circulating pentameric form. Furthermore, the four-amino acid C-terminal tail of FHL-1 (not present in FH) plays a role in mediating its binding to mCRP. PTX3 was found to be present in the macula of donor eyes and the AMD-associated Y402H polymorphism altered the binding of FHL-1 to PTX3. Our findings reveal that the binding characteristics of FHL-1 differ from those of FH, likely underpinning independent immune regulatory functions in the context of the human retina.

Original languageEnglish
Article number1643
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

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Complement Factor H
C-Reactive Protein
Inflammation
Proteins
Macular Degeneration
PTX3 protein
Retina
Tail
Complement System Proteins

ASJC Scopus subject areas

  • General

Cite this

C-reactive protein and pentraxin-3 binding of factor H-like protein 1 differs from complement factor H : Implications for retinal inflammation. / Swinkels, Maurice; Zhang, Justine H.; Tilakaratna, Viranga; Black, Graeme; Perveen, Rahat; McHarg, Selina; Inforzato, Antonio; Day, Anthony J.; Clark, Simon J.

In: Scientific Reports, Vol. 8, No. 1, 1643, 01.12.2018.

Research output: Contribution to journalArticle

Swinkels, Maurice ; Zhang, Justine H. ; Tilakaratna, Viranga ; Black, Graeme ; Perveen, Rahat ; McHarg, Selina ; Inforzato, Antonio ; Day, Anthony J. ; Clark, Simon J. / C-reactive protein and pentraxin-3 binding of factor H-like protein 1 differs from complement factor H : Implications for retinal inflammation. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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