Granulocyte–macrophage colony‐stimulating factor augments neutrophil‐mediated cartilage degradation and neutrophil adherence

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Abstract
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.

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