Frank a . Robey , Karen

C-reactive protein (CRP) 1 is the prototypical acute phase protein; serum levels of CRP increase by as much as 2,000-fold during the first 24-48 h after the onset of certain types of inflammation (1, 2). Although CRP was discovered over fifty years ago (3), subsequent studies have yet to uncover a unique function for CRP. It is believed that CRP resembles immunoglobulins because, when bound to certain ligands, it can promote reactions of precipitation (3, 4), complement fixation (5), and phagocytosis (6). Therefore , it has been reasonable to hypothesize a unique function for CRP involving any or all of these phenomena. Recently (4), chromatin was described as being a unique ligand for CRP; it was demonstra ted that binding of CRP to the nucleosome core particles, the basic structure present in chromatin, occurred with an affinity of at least 2,400times the affinity of CRP binding to any other previously described ligand. Chromatin is a term used to describe nuclear DNA complexed to its natural proteins, most of which are histones. Individually, DNA and histones are highly water-soluble substances because of the respective polyanionic and polycationic charges. However, chromatin itself is an insoluble, sticky material as a result of charge neutralization when the histones are electrostatically bound to DNA. In view of the wide range of inflammatory conditions in which insoluble chromatin might be released from damaged cells and in which CRP levels in serum are elevated, we sought methods to verify in vitro our previous hypothesis (4) about the in vivo function of CRP, namely, that it mediates the removal of chromatin from the body after cell death. In the present study, we performed experiments using the hemolytic activity of serum against sensitized sheep erythrocytes and chromatin containing [~H]DNA as an indicator of very complex events in serum brought on by CRP-chromatin complexes. We found an association between the degree o f chromatin solubilized by serum and the CRP concentration. Additionally, we found that some systemic lupus erythematosus (SLE) patients may have a depressed mechanism to solubilize chromatin, which A portion of this work was presented at the 1984 Workshop on Abnormal Cells, New Products and Risk, held at NIH, Bethesda, MD, July 31, 1984. z Abbreviations used in this paper: CRP, C-reactive protein; ELISA, enzyme-linked immunosorbent assay; PC, phosphorylcholine; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SLE, systemic lupus erythematosus; TLCK, N-a-p-tosyI-L-lysine chloromethyl ketone.