Faculty Bibliography

Monosodium urate crystals (MSU) have been shown to activate the alternative pathway of complement in a dose- and time-dependent fashion at 37 degrees C. Activation was maximal upon addition of 10-20 mg/ml monosodium urate crystals to C2-deficient human serum (C2D) or normal human serum containing 5 mM MgEGTA. Immunoelectrophoretic analysis of such treated sera demonstrated cleavage of C3 and factor B. Incubation of highly purified C3 and factor B with 10 mg/ml MSU did not, however, affect their immunoelectrophoretic pattern, suggesting that cleavage of either factor B or C3 in serum requires an intact alternative complement pathway. The fluid-phase control proteins, Factor H and Factor I, were not found to be diminished upon incubation of C2D serum or NHS containing MgEGTA with MSU. Thus activation appeared to be surface dependent and not a consequence of control protein depletion. It was also found, in agreement with earlier observations, that the classical complement pathway is activated, with concomitant depletion of C1 and C4. We conclude that MSU crystals activate both the classical and alternative pathways, and that such activation may participate in the pathogenesis of gouty arthritis.

Three scorpion venoms caused a transitory decrease in the rate of fluid secretion and increases in the concentration, in pancreatic juice, of total protein and individual enzymes. Protein and enzyme elevations 4-7 fold over the basal levels were produced by the venom of Tityus bahiensis and 6-7 fold by venoms from Tityus serrulatus and Buthus quinquestriatus. Although these increases were smaller than those stimulated by the C-terminal octapeptide of cholecystokin (OP-CCK; 8-9 fold), the secretory responses were of longer duration, so that the total output of protein caused by each of the three venoms was significantly greater than that observed with OP-CCK. Although electron microscopy revealed evidence of widespread degeneration of acinar cells at 1 hr and more extensive damage at 2 hr following injection of scorpion venom, no free protease was detected in pancreatic secretion collected during this period. The scorpion venoms also caused hypersecretion of viscid saliva. In contrast, rattlesnake venom, had no detectable effect on salivation, pancreatic secretion or morphology of the pancreas.

We studied the capacities of naked and protein-coated monosodium urate (MSU) crystals to stimulate superoxide anion (O(2)) release by human polymorphonuclear leukocytes (PMN). Uncoated MSU estimated significant O(2) production by cytochalasin B-treated PMN. Precoating MSU with IgG caused an increase in mean O(2) production, whereas precoating heated MSU with serum or plasma inhibited O(2) release. Unheated MSU crystals, which activate complement to a greater extent than heated crystals, also provoked O(2) generation, an effect again abrogated by precoating with serum but not with plasma. Coincubation of unheated MSU and plasma resulted in an enhancement of O(2) generation. The results of these experiments support the hypothesis that adsorbed proteins modulate the phlogistic potential of MSU and that the surface activation of humoral mediators contributes to the local inflammatory response