|Stephanie M Dorta-Estremera1,2 and Wei Cao1,2*|
|1Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA|
|2The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA|
|Corresponding Author :||Wei Cao
Department of Immunology
nit 902, The University of Texas
MD Anderson Cancer Center 7455
Fannin St., Houston TX 77054,USA
E-mail: [email protected]
|Received May 18, 2015; Accepted June 19, 2015; Published June 23, 2015|
|Citation: Dorta-Estremera SM, Cao W (2015) Human Pentraxins Bind to Misfolded Proteins and Inhibit Production of Type I Interferon Induced by Nucleic Acid-Containing Amyloid. J Clin Cell Immunol 6:332. doi: 10.4172/2155-9899.1000332|
|Copyright: © 2014 Cao W, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
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Objective: Amyloid deposition is linked to multiple human ailments, including neurodegenerative diseases, type 2 diabetes, and systemic amyloidosis. The assembly of misfolded proteins into amyloid fibrils involves an intermediate form, i.e., soluble amyloid precursor (AP), which exerts cytotoxic function. Insoluble amyloid also stimulates innate immune cells to elicit cytokine response and inflammation. How any of these misfolded proteins are controlled by the host remains obscure. Serum amyloid-P component (SAP) is a universal constituent of amyloid deposits. Shortchain pentraxins, which include both SAP and C-reactive protein (CRP), are pattern recognition molecules that bind to diverse ligands and promote the clearance of microbes and cell debris. Whether these pentraxins interact with AP and cofactor containing amyloid and subsequently impact their function is not known.
Methods and Results: To detect the interaction between SAP and different types of amyloids, we performed a dot blot analysis. The results showed that SAP invariably bound to protein-only, nucleic acid-containing and glycosaminoglycan-containing amyloid fibrils. This interaction required the presence of calcium. By ELISA, both SAP and CRP bound to soluble AP in the absence of divalent cations. Further characterization, by gel filtration, implied that SAP decamer may recognize AP whereas aggregated SAP preferentially associates with amyloid fibril. Although SAP binding did not affect cytotoxic function of AP, SAP potently inhibited the production of interferon-α from human plasmacytoid dendritic cells triggered by DNA-containing amyloid.
Conclusions: Our data suggest that short pentraxins differentially interact with various forms of misfolded proteins and, in particular, modulate the ability of nucleic acid-containing amyloid to stimulate aberrant type I interferon response. Hence, pentraxins may function as key players in modulating the pathogenesis of protein misfolding diseases as well as interferon-mediated autoimmune manifestation.
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