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Stimulation of human neutrophils, monocytes, and platelets by modified C-reactive protein (CRP) expressing a neoantigenic specificity

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Abstract

C-reactive protein (CRP) can be structurally modified by heat, acid, or urea-chelation to express a neoantigen designated by us as neo-CRP. This antigen is also expressed on the in vitro primary protein translation products of both human and rabbit CRP. Unmodified CRP and CRP complexed with pneumococcal C-poly-saccharide (CPS) do not express neo-CRP. Forms of CRP expressing neo-CRP but not native CRP antigenicity (even in the presence of CPS) consistently and in a dosedependent manner potentiated the respiratory burst response of human polymorphonuclear leukocytes and peripheral blood monocytes to heat-modified IgG. Forms of CRP expressing neo-CRP antigenicity also induced reactions of aggregation and secretion from isolated platelets and potentiated platelet activation stimulated by ADP in platelet-rich-plasma, while native CRP alone or complexed with CPS again did not. Unlike CRP-CPS complexes, forms of CRP expressing neo-CRP were not able to activate the complement system. These data emphasize the biologic potential inherent in this humoral acute-phase reactant, particularly in the activation of the formed elements of the blood important in the inflammatory response. Since these cell-activating properties are preferentially observed when CRP is structurally modified to express the neo-CRP antigen, such a molecular conversion may be central to the structure-function relationships of CRP at local sites of inflammation and tissue injury.

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Supported in part by Biomedical Research Support Grant 97881 (Rush Presbyterian St. Luke's Medical Center), R23AI23030 (National Institute of Allergy and Infectious Diseases) and HL-23457 (National Heart, Lung & Blood Institute). B.A.F. was the recipient of an NIH Research Career Development Award HL-00614. H.G. holds the Thomas G. Coogan, Sr. Chair in Immunology established by Marjorie Lindheimer Everett.

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Potempa, L.A., Zeller, J.M., Fiedel, B.A. et al. Stimulation of human neutrophils, monocytes, and platelets by modified C-reactive protein (CRP) expressing a neoantigenic specificity. Inflammation 12, 391–405 (1988). https://doi.org/10.1007/BF00915774

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