Granulocyte-macrophage colony-stimulating factor augments neutrophil-mediated cartilage degradation and neutrophil...

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is produced in large quantities by synoviocytes in the inflamed arthritic joint and is known to be a neutrophil activator. Neutrophils predominate during acute flares of arthritis and are important mediators of cartilage destruction. In this investigation, we show that treatment of neutrophils with 10-1,000 units/ml of GM-CSF augments their ability to degrade cartilage proteoglycan in vitro. This was associated with increased neutrophil adherence to cartilage and increased release of oxygen-derived reactive species and granule enzymes in response to cartilage. Coating the cartilage with heat-aggregated human immunoglobulin G (AHG) enhanced both neutrophil adherence to the tissue and tissue degradation. GM-CSF, however, augmented these neutrophil effects independently of the presence of AHG. In contrast, neutrophil-mediated inhibition of proteoglycan synthesis was unaffected by GM-CSF.