Plasma protein binding by monosodium urate crystals. Analysis by two-dimensional gel electrophoresis.

Using 2-dimensional O'Farrell gel electrophoresis, we have mapped the proteins from undiluted plasma and serum which bind to monosodium urate (MSU) crystals. More than 30 crystal-associated polypeptides were visualized, including anionic and cationic species. Proteins increased on the crystals relative to plasma included C1q, C1-r, C1-s, fibronectin, fibrinogen, and kininogen. Crystal-bound polypeptides derived from IgG, albumin, and transferrin were recovered in decreased amounts relative to plasma. Direct evidence for activation of the complement and coagulation systems in plasma was provided by the identification of crystal-associated activation fragments of C1 and kininogen. Plasmas deficient in selected proteins (e.g., C1q and IgG) were used to define the role of these proteins in such activation events and confirmed activation of C1 in immunoglobulin-deficient plasma by MSU crystals. In summary, we have described a high resolution, semiquantitative approach to analyze protein binding to crystals, have documented the complexity of crystal-plasma protein interaction, and have provided direct evidence for the binding of coagulation system proteins and binding and activation of complement by MSU crystals, in whole plasma and IgG-deficient plasma.