Characterization of neutrophil-mediated degradation of human C-reactive protein and identification of the protease.

Human C-reactive protein (CRP) is shown to mediate a release of enzymatic activity from neutrophils which promotes its own degradation in the extracellular medium. This egress of proteolytic activity, which was upregulated by phorbol 12-myristate 13-acetate (PMA), was found to occur from both the cytoskeleton and membrane fractions of neutrophils and was dependent on the time of incubation of CRP with the cells and the concentration of CRP. Neutrophil kinases activated by PMA are found to be involved in upregulating the activity of the CRP-degrading protease. The apparent molecular weight of the CRP-degrading protease associated with the conditioned medium from PMA-stimulated neutrophils and neutrophil membrane and cytoskeleton preparations, was found by size exclusion chromatography to be 600 kD and migrated on 3-13% SDS-PAGE as four discrete bands to positions corresponding to apparent molecular weights of 209 kD, 316 kD, 398 kD and 501 kD.