ACTIVATION OF NEUTROPHILS BY SOLUBLE AND INSOLUBLE IMMUNOGLOBULIN AGGREGATES FROM SYNOVIAL-FLUID OF PATIENTS WITH RHEUMATOID-ARTHRITIS

Objectives-Previous work has shown that synovial fluid isolated from p atients with active rheumatoid arthritis contains soluble (not sedimen ted by centrifugation at 11 600 g for two minutes) and insoluble (sedi mented by centrifugation at 11 600 g for two minutes) immunoglobulin a ggregates that are capable of activating reactive oxidant production b y blood-stream neutrophils. The purpose of this study was to determine which of these types of immunoglobulin aggregates activated the secre tion of reactive oxygen metabolites and granule enzymes from neutrophi ls. Methods-Cell free synovial fluid (from patients with rheumatoid ar thritis) was added to neutrophils isolated from blood of healthy contr ols that had been incubated in the presence and absence of granulocyte -macrophage colony stimulating factor (GM-CSF). Reactive oxidant produ ction was measured by luminol chemiluminescence (which detects both in tracellular and extracellular oxidant production) and by cytochrome c reduction (which measures superoxide secretion). Results-The soluble a ggregates only activated neutrophils that were previously primed, and activated a rapid and transient burst of reactive oxidant secretion. O n the other hand, the insoluble aggregates activated primed and unprim ed neutrophils with similar efficacy and most of the oxidants generate d (especially in unprimed cells) were intracellular. The soluble aggre gates, but not the insoluble aggregates, also activated the secretion of myeloperoxidase from neutrophils that had either been pretreated wi th cytochalasin B or primed with GM-CSF. Conclusion-It is thus propose d that these soluble immunoglobulin aggregates are responsible for act ivation of the release of tissue damaging granule enzymes and reactive oxidants from primed neutrophils within the rheumatoid joint.