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.

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Journal Scientific Reports
Swinkels, M. (Maurice), Zhang, J.H. (Justine H.), Tilakaratna, V. (Viranga), Black, G. (Graeme), Perveen, R. (Rahat), McHarg, S. (Selina), … Clark, S.J. (Simon J.). (2018). C-reactive protein and pentraxin-3 binding of factor H-like protein 1 differs from complement factor H: Implications for retinal inflammation. Scientific Reports, 8(1). doi:10.1038/s41598-017-18395-7