Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
C-Reactive Protein Binds and Induces Phagocytosis through FcRI
Marjon1, Kristopher D., Lu2, Jinghua, Marnell1, Lorraine L., Park1, Kye S., Mold1, Carolyn, Sun2, Peter D., Du Clos3, Terry W.
University of New Mexico, Albuquerque, NM
National Institute of Allergy and Infectious Disease. Rockville, MD
VA Medical Center, Albuquerque, NM
Purpose:
C-reactive protein (CRP) is an acute phase serum pentraxin and its serum concentration can increase up to a thousand fold due to inflammatory stimuli. Pentraxins such as serum amyloid P component (SAP) and CRP have been shown to interact with the FcgR family. FcaRI is a receptor for IgA that is functionally related to FcgR, but has a higher sequence homology and structural similarity to members of the leukocyte receptor complex. FcaRI plays a role in IgA-mediated host defense and immunoregulation. FcaRI is expressed on neutrophils, eosinophils, monocytes, and dendritic cells. The purpose of this study was to determine if CRP functionally interacts with an additional immunoglobulin receptor such as FcaRI.
Methods:
CRP or IgA binding affinity to FcaRI was quantitatively measured by surface plasmon resonance (SPR). CRP and IgA binding to rat basophilic leukemia (RBL) cells and FcaRI-transfected RBL (G248) cells was measured by flow cytometry. FcaRI mediated degranulation of RBL and G248 cells was measured using a colorimetric assay for b-hexosaminidase release. CRP-mediated phagocytosis was measured using human neutrophils and CRP-opsonized FITC labeled Streptococcus pneumoniae type 27 (Pn27). Phagocytosis was measured by flow cytometry using intracellular fluorescence of neutrophils after quenching extracellular bacterial fluorescence with trypan blue. Specificity of CRP mediated phagocytosis though FcaRI was established by inhibition with anti-FcaRI mAb MIP8a.
Results:
We report that CRP interacts with FcaRI with micromolar affinity and induces cellular responses. CRP bound to G248 cells and was inhibited by MIP8a, a well characterized mAb that blocks IgA binding to FcaRI, to the level of background binding to untransfected RBL cells. CRP also induced degranulation in G248 cells comparable to IgA induced degranulation. SPR studies confirmed the binding interaction between CRP and FcaRI and also demonstrated that C1q inhibited CRP binding to both FcaRI and FcgRIIa. IgA and CRP do not compete for FcaRI but are both inhibited by MIP8a. To investigate the role of this interaction further we used human neutrophils to determine if CRP could induce phagocytosis of heat-killed S. pneumoniae type 27. We found that CRP increased the phagocytic index above background and that CRP-mediated phagocytosis was inhibited by MIP8a.
Conclusion:
These findings shed light on a novel interaction for CRP and FcaRI and give insight into a functional role between the two. This study broadens the functional role for CRP in innate immunity and identifies FcaRI as an additional CRP receptor on neutrophils.
To cite this abstract, please use the following information:
Marjon, Kristopher D., Lu, Jinghua, Marnell, Lorraine L., Park, Kye S., Mold, Carolyn, Sun, Peter D., et al; C-Reactive Protein Binds and Induces Phagocytosis through FcRI [abstract]. Arthritis Rheum 2009;60 Suppl 10 :152
DOI: 10.1002/art.25235
