Monosodium urate monohydrate crystal-induced inflammation in vivo: quantitative histomorphometric analysis of cellular events

Arthritis Rheum. 2002 Jun;46(6):1643-50. doi: 10.1002/art.10326.


Objective: To quantify the inflammatory cell response in rat air pouch pseudosynovial membrane during monosodium urate monohydrate (MSU) crystal-induced 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Count
  • Crystallization
  • Disease Models, Animal
  • Exudates and Transudates / cytology
  • Exudates and Transudates / immunology
  • Fibroblasts / cytology
  • Fibroblasts / immunology
  • Gout / chemically induced
  • Gout / immunology*
  • Gout / pathology*
  • Inflammation / chemically induced
  • Inflammation / pathology
  • Macrophages / cytology
  • Macrophages / immunology
  • Mast Cells / cytology
  • Mast Cells / immunology
  • Monocytes / cytology
  • Monocytes / immunology
  • Neutrophils / cytology
  • Neutrophils / immunology
  • Rats
  • Rats, Sprague-Dawley
  • Synovial Membrane / immunology
  • Synovial Membrane / pathology
  • Uric Acid / chemistry
  • Uric Acid / pharmacology*


  • Uric Acid