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Cartilage degradation by polymorphonuclear leucocytes: in vitro assessment of the pathogenic mechanisms
A R Moore1, H Iwamura, J P Larbre
1Department of Experimental Pathology, William Harvey Research Unit, St Bartholomew's Hospital Medical College, London, United Kingdom.
Abstract:
Polymorphonuclear leucocytes (PMNs), which predominate in inflammatory synovial fluid, can degrade cartilage. This was measured by a novel in vitro model; PMNs were incubated for up to one hour with 2 or 3 microns sections of cartilage and the glycosaminoglycan loss determined by microdensitometry after alcian blue staining. Glycosaminoglycan loss could be as a result of damage from reactive oxygen species, proteolytic enzymes, or a combination of the two. The relative contributions of these mechanisms were evaluated using selective inhibitors. The results show that activated PMNs will degrade cartilage and that this degradation is due to proteolytic enzymes and not reactive oxygen species. There is a specificity involving elastase but not other serine proteases. It is suggested that enzyme inhibition may play a part in reducing PMN mediated cartilage damage.
Insights
Activated white blood cells called polymorphonuclear leucocytes (PMNs) degrade cartilage through proteolytic enzymes, not reactive oxygen species. Enzyme inhibition may reduce this damage, offering potential therapeutic strategies for inflammatory joint conditions.
Area of Science:
- Biochemistry
- Immunology
- Rheumatology
Background:
- Polymorphonuclear leucocytes (PMNs) are key inflammatory cells in synovial fluid.
- Cartilage degradation is a hallmark of inflammatory joint diseases.
- The mechanisms by which PMNs damage cartilage are not fully elucidated.
Purpose of the Study:
- To investigate the role of PMNs in cartilage degradation.
- To differentiate the contributions of reactive oxygen species and proteolytic enzymes in PMN-mediated cartilage damage.
Main Methods:
- A novel in vitro model using PMNs and cartilage sections (2-3 microns).
- Measurement of glycosaminoglycan loss via microdensitometry after Alcian blue staining.
- Evaluation of reactive oxygen species and proteolytic enzyme involvement using selective inhibitors.
Main Results:
- Activated PMNs significantly degrade cartilage in vitro.
- Cartilage degradation is mediated by proteolytic enzymes, not reactive oxygen species.
- Elastase, a specific serine protease, plays a crucial role in this degradation.
Conclusions:
- Proteolytic enzymes released by PMNs are responsible for cartilage damage.
- Elastase is a key enzyme in PMN-mediated cartilage degradation.
- Enzyme inhibition strategies could be beneficial in managing PMN-induced cartilage damage.