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What turns neutrophils on

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Insoluble and soluble immune complexes in synovial fluid in rheumatoid arthritis activate neutrophils differently, researchers in Liverpool, UK, have found. Immune complexes and neutrophils are abundant in synovial fluid in rheumatoid arthritis, as are cytokines, which can prime neutrophils making them more responsive. Understanding how immune complexes and neutrophils interact, leading to production of tissue damaging enzymes and oxidants, and the molecular control of the interactions are potential keys to new therapeutic treatments.

Fossati et al used in vitro chemiluminescence to detect production of oxidants by washed blood neutrophils in their unprimed state or primed with granulocyte-macrophage colony stimulating factor—a cytokine in synovial fluid in rheumatoid arthritis—when incubated with synthetic insoluble or soluble immune complexes. By comparing the reaction kinetics of chemiluminescence with substrates available to the neutrophils either extracellularly or intracellularly and with different specific scavengers of oxidants, they were able to unravel the processes.

Insoluble complexes activated unprimed or primed neutrophils to produce oxidants that remained intracellular whereas soluble complexes reacted only with primed neutrophils but did so rapidly and transiently, the oxidants being secreted. Insoluble complexes also required FcyRIIIb but not FcyRII function whereas soluble complexes required both. In tests to detect granule enzymes insoluble complexes activated secretion with unprimed or primed neutrophils, although the reaction kinetics differed from those for the oxidants. Soluble complexes activated secretion only with primed neutrophils, leading the researchers to conclude that neutrophil activation occurs by different pathways for insoluble or soluble immune complexes and can be significantly affected by cytokines.