STREPTOCOCCAL CELL WALL-INDUCED ARTHRITIS - REQUIREMENTS FOR NEUTROPHILS, P-SELECTIN, INTERCELLULAR-ADHESION MOLECULE-1, AND MACROPHAGE-INFLAMMATORY PROTEIN-2

Immune arthritis in rat ankle joints was induced by intra-articular in jection of streptococcal cell wall extract (SCW), followed 21 days lat er by i,v, injection of SCW, This results in a monoarticular arthritis characterized by an influx of neutrophils and mononuclear cells, a 35 -fold increase in urinary excretion of 8-hydroxy-deoxyguanosine (8-OH- dGUA; an index of free radical production), ankle edema, and joint dam age/destruction. Neutrophil depletion substantially reduced the intens ity of ankle edema, Ab-induced blockade of P-selectin or ICAM-1 also r educed the intensity of ankle edema and the influx of neutrophils, Blo ckade of TNF-alpha or IL-1 resulted in nearly complete and persistent reduction in ankle edema and profound reductions in the accumulation o f neutrophils and mononuclear cells in affected joints. Finally, block ing of macrophage-inflammatory protein-2 reduced ankle edema and neutr ophil accumulation during the first 2 days after i,v, challenge with S CW, These data indicate that SCW-induced arthritis is neutrophil depen dent and that the recruitment of neutrophils and subsequent joint edem a requires ICAM-1, P-selectin, and macrophage-inflammatory protein-2, as well as TNF-alpha and IL-1.