Granulocyte-macrophage colony-stimulating factor augments neutrophil-mediated cartilage degradation and neutrophil adherence.
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.
Kowanko
I C
IC
Department of Immunology, Adelaide Children's Hospital, Australia.
Ferrante
A
A
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects*; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D011509:Proteoglycans / Q000037:antagonists & inhibitors / Q000378:metabolism; D012016:Reference Values
D011509:Proteoglycans; D016178:Granulocyte-Macrophage Colony-Stimulating Factor