During the interaction of fibroblasts and leukocytes in vitro, there was a two-to sixfold increase in the total amount of hyaluronate formed, and a corresponding increase in the rate (pg./cell/day) of hyaluronate synthesis. Increased glucose uptake from the culture medium (two-to fourfold) was associated with stimulation of hyaluronate formation. Cultures receiving leukocytes suffered an 8 to 33 per cent decrement in the fibroblast population. Leukocytes themselves con-WFWRODUCTION of joint fluid hyaluronic 0 acid by rheumatoid synovial tissue can be visualized as a consequence of altered synthetic activity of specialized connective tissue cells functioning in an abnormal milieu of infiltrating lymphoid cells and polymorphonuclear leukocytes ( PMN) .
To explore the nature of possible interactions between such diverse cell types, we established monolayer cultures of human fibroblasts from normal and rheumatoid articular tissue and incubated these cultures with isolated leukocytes. The peripheral blood leukocytes were isolated from normal persons and rheumatoid patients, and the lymphocyte-rich fractions and PMN-rich fractions which were prepared were added to monolayer fibroblast CUE tures to simulate the cell mixtures found in the inflamed synovial membrane.