THE EFFECT OF ACUTE-PHASE PROTEINS ON CLEARANCE OF CHROMATIN FROM THECIRCULATION OF NORMAL MICE

The clearance of nucleosome core particles and H1-stripped chromatin f rom the circulation of mice was examined. Radiolabeled chromatin prepa rations were injected into mice, and blood samples were obtained over 60 min. The animals were then killed, and the selected organs were col lected and radioactivity was measured, The acute phase response (APR) was induced by i.p. injections of casein before some clearance studies . Serum amyloid P component, the major acute phase protein in mice, in creased from 27 mu g/ml to 339 mu g/ml during the acute phase, The rat e of chromatin clearance decreased during the acute phase in C57BL/10J mice, At 5 min, 18% +/- 3% of the originally measured radioactivity r emained in control animals compared with 49% +/- 2% in acute phase ani mals (p < 0.001). Co-injection of either serum amyloid P component or C-reactive protein, the major acute phase protein in humans, caused a decrease in the rate of chromatin clearance similar to that observed f ollowing the induction of the APR, APR induction also caused a higher percentage of the chromatin to localize in the liver compared with the spleen, with the ratio changing from 10.2 +/- 0.7 to 16.1 +/- 1.9 (p < 0.004), In addition, the APR caused a decrease in the percentage of chromatin localized in the kidney. The lack of radioactivity associate d with cells in the circulation indicates that complement is not a maj or factor in the clearance mechanism of chromatin. These findings sugg est that the APR produces major changes in the rate and path of chroma tin clearance, These changes may protect against deposition of chromat in in target organs of systemic lupus erythematosus.