Incubation of monosodium urate crystals (MSUC) with normal human serum (NHS) resulted in the production of a factor chemotactic for neutrophils which was inactivated by monospecific antiserum to human C5, indicating it to be a product of C5 activation. When MSUC were incubated with NHS containing radioiodinated C5, a significant portion of the label was incorporated into a 1 × 106 MW, fluid phase complex identified as SC5b-9. The complex had a sedimentation velocity of 23.5 S and contained C5b as demonstrated by radioautography of reduced SDS-polyacrylamide electrophoretic slab gels. In addition, urate crystals preincubated with C5-deficient human serum, followed by extensive washing, were able to convert highly purified C5 to C5b. While purified C5 readily adsorbed to urate crystals, it was not activated to C5b in the absence of a fully functional complement cascade. These data provide direct evidence for the assembly of a complement C5 convertase enzyme on the surface of MSUC during incubation of crystals with human serum. The convertase then mediates C5 activation to C5a and C5b with resultant assembly of the fluid phase SC5b-9 complex. These observations further clarify the nature of MSUC-complement interactions and provide a mechanism for complement-mediated neutrophil chemotaxis in gout.
ASJC Scopus subject areas
- Immunology and Allergy
- Pathology and Forensic Medicine