CHANGES IN THE PROTEINS COATING MONOSODIUM URATE CRYSTALS DURING ACTIVE AND SUBSIDING INFLAMMATION - IMMUNOGOLD STUDIES OF SYNOVIAL-FLUID FROM PATIENTS WITH GOUT AND OF FLUID OBTAINED USING THE RAT SUBCUTANEOUS AIR POUCH MODEL

Objective. In this in vivo study, we investigated changes in the prote ins that coat monosodium urate (MSU) crystals in human synovial fluid samples and rat air pouch fluid samples obtained sequentially during p eriods of active and resolving inflammation, in order to evaluate whet her in vivo findings are consistent with hypotheses on roles of protei n coating based on in vitro findings. Methods. Crystals from patients with gout were isolated from joint fluids with acute inflammation, and subsequently from the same joints at the time inflammation was resolv ing. Crystals were also obtained using the rat subcutaneous air pouch model. Immunogold was used to label proteins coating MSU crystals, for light microscopy (LM) and transmission electron microscopy (TEM) stud ies. Results. Dense immunogold-silver labeling for IgG was observed un der LM on crystals from fluid with acute inflammation, whereas other p roteins (apolipoproteins [Apo], fibronectin, fibrinogen, albumin) were not labeled significantly. Apo B became strongly positive on crystals as the inflammation subsided, whereas other proteins were only weakly positive and IgG became absent or weakly positive. Quantitative TEM e valuation confirmed the LM observations. Conclusion. This study provid es the first in vivo evidence supporting the notion derived from previ ous in vitro studies that proteins coating MSU crystals change as infl ammation evolves. Protein coatings may play an important role in the s elf-limited nature of gouty inflammation. IgG coating MSU crystals may enhance the inflammation. As the inflammation subsides, Apo B could d isplace the IgG by competitively coating sites on crystals and could c ontribute in part to the resolution of the acute gouty arthritis.