Impairment of neutrophil Fc gamma receptor mediated transmembrane signalling in active rheumatoid arthritis.
Neutrophil Fc gamma receptor (Fc gamma R) signalling responses were compared in healthy subjects, patients with definite rheumatoid arthritis (RA), ankylosing spondylitis, and osteoarthritis. The patients with A were subdivided into those with active synovitis and those with quiescent disease. Basal intracellular calcium ion concentrations in patients with inactive RA were significantly higher than in control subjects, which in turn were greater than in patients with active RA. Transient cytosolic calcium ion fluxes were observed after binding Fc gamma RII or Fc gamma RIII with specific monoclonal antibodies and cross linking with the F(ab')2 fragment of antimouse IgG. Response times were significantly faster for Fc gamma RII than for Fc gamma RIII. Peak concentrations of intracellular calcium ions after neutrophil stimulation were comparable for Fc gamma RII and RIII in healthy subjects. Neutrophils in patients with ankylosing spondylitis and osteoarthritis responded to Fc gamma R triggering, but in the group with active RA fluxes of calcium ions were severely depressed. Neutrophils isolated from patients with RA with quiescent disease showed exaggerated responses when compared with controls. Expression of all three Fc gamma R types on neutrophils from patients with active RA, as measured by monoclonal antibody binding, was comparable with control cells. Impairment of neutrophil Fc gamma R cytosolic signalling in active RA could reflect a receptor signalling defect with potential effects on Fc mediated functions, or a fundamental defect in calcium ion homeostasis within these cells.
Goulding
N J
NJ
Bath Institute for Rheumatic Diseases, United Kingdom.
Guyre
P M
PM
D000328:Adult; D015703:Antigens, CD / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010003:Osteoarthritis / Q000276:immunology / Q000378:metabolism; D011961:Receptors, Fc / Q000276:immunology*; D017452:Receptors, IgG; D015398:Signal Transduction / Q000276:immunology* / Q000502:physiology; D013167:Spondylitis, Ankylosing / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; D011961:Receptors, Fc; D017452:Receptors, IgG; D002118:Calcium