title: Adhesion and TNF priming in neutrophil-mediated cartilage damage.
abstract: Neutrophils predominate in the acute stages of rheumatoid arthritis and are implicated in the cartilage damage which is characteristic of this disease. In vitro neutrophils can be primed for increased ability to damage host tissues by a number of cytokines including tumor necrosis factor-alpha (TNF). The role of adherence in this process was investigated. Opsonization of cartilage with aggregated IgG (HAGG) and complement promoted neutrophil damage to cartilage. Adherence was increased by HAGG and TNF. Separation of neutrophils from cartilage markedly reduced the neutrophil-mediated injury and abolished the priming effect of TNF. Inactivation of complement or antibodies against CD11a or CD11b reduced neutrophil-mediated cartilage damage and markedly reduced TNF-priming of this damage and yet did not alter adherence of control or TNF-primed cells. These results suggest that neutrophil damage to cartilage is promoted by agents that favor adherence. The failure to block adhesion of neutrophils by complement inactivation or antibodies to CD11a or CD11b suggests that neutrophil adherence to cartilage occurs simultaneously through several different receptors. The massive reduction of TNF enhancement of neutrophil damage to cartilage by preventing adhesion suggests that adherence is required for this action of TNF.
authors.affiliation: Department of Immunology, Women's and Children's Hospital, Adelaide, Australia .
authors.forename: I C
authors.initials: IC
authors.lastname: Kowanko
authors.forename: A
authors.initials: A
authors.lastname: Ferrante
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000276:immunology*; D002417:Cattle; D002448:Cell Adhesion; D003165:Complement System Proteins / Q000502:physiology; D046508:Culture Techniques; D006358:Hot Temperature; D016023:Integrins / Q000502:physiology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D009895:Opsonin Proteins; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D016023:Integrins; D009895:Opsonin Proteins; D014409:Tumor Necrosis Factor-alpha; D003165:Complement System Proteins