Role of monocytes in cryoglobulinemia-associated nephritis

Several monocyte-macrophage functions were found to be defective in cryoglobulinemic patients. Nevertheless, monocytes actively phagocytizing cryoglobulins have been frequently found in kidney specimens from these patients. Whether subsequent degradation of the ingested immune material is effective, however, is still unknown. Monocytes from eight cryoglobulinemic patients (4 with active disease and associated nephritis and 4 inactive cases without nephritis) and eight normal controls of same sex and similar age were analyzed. Monocytes from patients with active cryoglobulinemia and associated nephritis were found to be able to ingest, but unable to catabolize, cryoglobulins, as shown by electron microscopy using gold-labeled goat IgG to human IgG and IgM in 18-hour cultured suspensions. Synthesis and maturation of monocyte cathepsin D, one of the most important lysosomal proteases, were analyzed in the same subjects. Purified monocytes were cultured in presence or absence of cryoglobulins for 18 hours at 37 degrees C in RPMI medium and labeled with 35S-methionine. The various forms of cathepsin D were separated by electrophoresis and visualized by fluorography. Results from cultures of monocytes from clinically active cryoglobulinemic patients with nephritis suggest that intracellular transport of newly synthesized cathepsin D was impaired and the release into the medium of precursor polypeptides of the enzyme enhanced in each experimental condition. Since procathepsin D is susceptible to activation in pathologic conditions lowering local pH (such as in inflamed tissues), these data suggest that monocytes from patients with active cryoglobulinemia and associated nephritis have a propensity to exert phlogistic effects via secretion of procathepsin D in tissues.