The generation of polymorphonuclear cell (PMN) superoxide ion (02-) by monosodium urate (MSU) crystals may be important in the pathogenesis of acute gout. Coating MSU crystals with IgG prior to exposure to PMN markedly augmented 02-generation. This augmentation was inhibited by supernates, termed cell lysate, derived from sonicated PMN or PMN exposed to MSU crystals for 5 hours at 37°C. Lysate was effective in inhibiting 02-production when incubated with MSU crystals prior to, during, or after MSU crystals were exposed to IgG. No IgG could be eluted from crystals exposed to both lysate and IgG. Immunoelectron microscopy showed virtually no IgG on crystal surfaces after incubation of crystals with lysate and IgG. These data suggest that products of PMN injury can modulate further PMN responses to MSU crystals. This phenomenon provides a negative feedback loop and is one possible mechanism for the self-limitation of acute gouty attacks. Recent studies have documented the ability of monosodium urate (MSU) crystals to bind a variety of proteins (1-8). It is believed that cationic proteins preferentially bind to MSU crystals because of the anionic charge of the crystal surface (5,6). The theory that protein binding is an in vivo phenomenon is supported by the results of studies by Hasselbacher and Schumacher, who demonstrated that immunoglobulin and fibrin were bound to MSU crystals that were obtained from tophi (7). Cherian and Schumacher also demonstrated, by immunoelectron microscopy, immunoglobulin coatings on crystals in phagosomes of cells from synovial fluid (8). That protein binding may have functional significance was shown by Abramson et a1 (l), who demonstrated that production of superoxide ion (02-) by polymorphonuclear cells (PMN) exposed to IgG-coated MSU crystals was significantly greater than the production by cells exposed to uncoated crystals. Kozin et a1 (9) found that IgG-coated MSU crystals produced less early PMN lysis, as measured by lactate dehydrogenase release, while PMN phagocytosis of MSU crystals, as measured by lysozyme release, was increased.The above findings are consistent with the theory of the pathogenesis of gout as postulated by several authors (10,ll). At the initiation of the gouty attack, IgG and, possibly, other proteins are bound to MSU crystals. The protein coating prevents PMN lysis and enhances phagocytosis of the crystals; the crystal is then engulfed in a phagosome (12), and the protein coating is stripped off by lysosomal enzymes. The now uncoated crystals lyse the lysophagosomal membrane, releasing lysosomal enzymes into the cytoplasm of the cell and causing cell injury and death.

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