DIFFERENCES IN OXIDATIVE RESPONSE OF SUBPOPULATIONS OF NEUTROPHILS FROM HEALTHY-SUBJECTS AND PATIENTS WITH RHEUMATOID-ARTHRITIS

Objectives-To determine whether blood neutrophils from healthy individ uals and blood and synovial fluid neutrophils from patients with rheum atoid arthritis (RA) responded differently to priming agonists and sti muli of the oxidative burst and, if so, whether this was a property of a sub-population of neutrophils. Methods-Continuous flow electrophore sis was used to separate neutrophils into subpopulations based upon qu antitative differences in net negative surface charge. The generation of superoxide anion (O-2(-)) was used as a measure of oxidative activi ty using 10(-7) mol/l N-formyl-methionylleucyl-phenylalanine (FMLP) as the stimulating agonist and 10(-8) mol/l platelet activating factor ( PAF) as the priming agent. Results-The production of O-2(-) by blood a nd synovial fluid neutrophils from RA patients in response to FMLP was greater than that observed with control blood neutrophils (p < 0.001) . Priming of normal blood neutrophils with PAF increased their FMLP in duced oxidative burst (p < 0.001), but PAF treatment had no effect on rheumatoid neutrophils. Neutrophils from synovial fluid of RA patients were less electronegative than paired blood samples and exposure of b lood neutrophils to FMLP but not PAF reduced their surface charge. Con tinuous flow electrophoresis isolated three neutrophil subpopulations: cells of least surface electronegativity were ascribed to pool P1 and cells of greatest surface electronegativity to P3. Normal blood neutr ophils from P3, but not P1, showed increased oxidative activity after PAF priming (twofold increase; p < 0.01), whereas the responsiveness o f rheumatoid blood and synovial fluid neutrophils from P1 and P3 was n ot modified by PAF treatment under the same conditions. Conclusion-It is suggested that most of the circulating neutrophils in RA are alread y in a state of readiness to generate O-2(-) upon activation by an inf lammatory stimulus. This is in contrast to normal blood neutrophils, w hich have both non-responsive subpopulations with respect to priming a gonists.