Humoral mechanisms are supported by the demonstration of local rheumatoid factor production within the synovium, the formation of IgM-activated B cells and IgG immune complexes, and activation and consumption of complement via the classic pathway. The sequelae of complement activation include increased vascular permeability and phagocytosis of the immune complexes by phagocytic cells. Aggregates of immune complexes within polymorphonuclear leukocytes are often seen in rheumatoid synovial fluid and have been termed "RA cells" or "ragocytes." Antigen-antibody complexes formed within the joint cavity can become trapped in hyaline cartilage and fibrocartilage, where they cause changes in matrix macromolecules. Within the synovial fluid, immune complexes activate the complement system, kinins, phagocytic cells, and the release of lysosomal enzymes and oxygen free radicals. Mediators produced in this process stimulate synovial cells to proliferate and produce proteinases and prostaglandins. These products cause dissolution of connective tissue macromolecules, as well as articular cartilage. They may also activate fibroblasts to produce a denser connective tissue matrix (fibrosis).