The role of the neutrophil in rheumatoid arthritis.

Neutrophils acquire lysosomal granules and assembly systems for producing soluble mediators of inflammation during the process of maturation in the bone marrow. Subsequently, they emigrate from the circulation when they become attracted to joint spaces of rheumatoid arthritis patients by chemoattractants such as the complement split product, C5a, and leukotriene B4. Exposure to immune complexes, rheumatoid factor, and cytokines in the synovial fluid results in neutrophil activation with release of granule contents, toxic oxygen metabolites, and proinflammatory products of the arachidonic acid cascade. This process is analogous to a local Arthus reaction in which activation of the complement system is a central event. Some of the inflammatory materials released by this reaction contribute to the cartilage destruction seen in rheumatoid arthritis. Because others are chemoattractants themselves, they perpetuate intraarticular inflammation and permit the predominance of acute inflammatory cells in lesions maintained by chronic inflammation.