Monosodium urate monohydrate crystal–induced inflammation in vivo: Quantitative histomorphometric analysis of cellular events

Abstract

Objective. To quantify the inflammatory cell response in rat air pouch pseudosynovial membrane during monosodium urate monohydrate (MSU) crystalinduced inflammation.Methods. In the rat air-pouch model, we used a computer-assisted histomorphometric method to quantify cell distributions, based on cell linear densities, in histologic sections of membranes from pouches injected with MSU or saline. The volume, white blood cell (WBC) count, and histamine content of the pouch exudates were determined at several time points.Results. Injection of 10 mg of MSU crystals into the pouch produced an acute exudate. After peaking at 24 hours, the exudate volume and WBC count decreased spontaneously over the next 3 days, simulating the self-limited course of acute gout. Membrane thickness followed a parallel course. Membrane polymorphonuclear cell (PMN) linear densities were closely correlated with exudate WBC counts, suggesting PMN recruitment from the subintimal synovial membrane. Both monocyte/macrophage and mast cell linear densities increased in the subintimal layer 2 hours after crystal injection (P ‫؍‬ 0.038 and P ‫؍‬ 0.03, respectively, versus controls), whereas PMN linear densities showed 2 peaks, one at 4 hours and the other 24 hours. The exudate histamine content peaked 6 hours after crystal injection, when mast cell linear densities were minimal in the membranes, suggesting mast cell degranulation.Conclusion. An increase in monocyte/macrophage and mast cell densities in the membrane preceded the PMN influx in the pouch membrane and exudate, suggesting that mast cells may be involved in the early phase of MSU crystal-induced inflammation, at least in this rat model.The pathogenesis of acute gout has been addressed in many studies. Synthetic monosodium urate monohydrate (MSU) crystals have been injected into the tissues or joints of various animals, including dogs (1), rats (2), mice (3), and rabbits (4). These in vivo experiments have elucidated the kinetics of acute-phase proteins, cytokines, and polymorphonuclear cell (PMN) and mononuclear cell (MNC) contents in exudates, showing a peak in cell recruitment and demonstrating that the acute phase was followed by self-limitation of the MSU crystal-induced inflammation. In vitro studies have shown that MSU crystals added to various cell cultures (5) induced time-and dose-dependent cytokine secretion. Schumacher et al (1) and Gordon et al (6) have reported evidence that acute gout is initiated by phagocytosis of free MSU crystals by the lining cells (type A [macrophage-like] synovial cells). This event is currently acknowledged to precede synovial inflammation per se (7,8). However, little is known about the kinetics of the cellular events within the synovial membrane.

Preparation and <i>in Vitro</i>, <i>in Vivo</i> Characterization of Elastic Liposomes Encapsulating Cyclodextrin-Colchicine Complexes for Topical Delivery of Colchicine

“…Evaluation of Biological Anti-gout Activity In vivo performance of diŠerent colchicine formulations was evaluated by MSU-induced rat air pouch model. 32) Edema is a characteristic feature of in‰am-mation that was measured in terms of exudate volume in the present study. Results of exudate volume and leukocyte count are indicators of in‰ammation in joint spaces and their increase is proportional to the severity of in‰ammatory condition.…”

Inhibition of monosodium urate crystal-induced inflammation by scopoletin and underlying mechanisms

“…Infiltration of vast numbers of neutrophils into inflamed joints is the hallmark of acute gouty arthritis. However, cellular kinetic analysis using rat air pouch model of gout indicates that an increase in monocytes/ macrophages density precedes the neutrophil influx [22]. Recent studies also implicate innate cells of monocyte/macrophage lineage as playing a governing role in the pathogenesis of gout [23,24].…”

Anti-inflammatory and anti-hyperuricemia properties of chicken feet cartilage: treatment on gouty arthritis animal model

“…Indomethacin, a non-steroidal anti inflammatory drugs (NSAID) often prescribed for gout patients, also reduced CD11b + TNF-α dan CD11b + IL-6 level in spleen. Those cytokines were produced by various cells, including synovial cells, monocytes-macrophages, and neutrophils, and were well known to propagate a local or sistemic inflammatory response (Liu-Bryan and Lioté, 2005;Inokuchi et al, 2008;Schiltz et al, 2002). It can be stated that AE and CFE inhibits proinflammatory cytokines via NFκB-dependent mechanism.…”