Connective tissue activation

Human synovial fibroblasts in culture have been stimulated to augment hyaluronate synthesis and glucose utilization by connective tissue activating peptides (CTAP) extracted from human spleen, lymphocytes, platelets, granulocytes, and tumor cells. The platelet‐derived mediator CTAP‐III also stimulated DNA synthesis in synovial fibroblasts, but CTAP‐I from lymphocytes and spleen did not. The present study demonstrates the mitogenic potential of a granulocyte mediator (CTAP‐PMN). Normal granuiocytes were prepared with Ficoll‐diatrizoate gradients, platelet contamination being estimated by phase microscopy and by radioimmunoassay for the platelet‐specific protein, β thromboglobulin. CTAP‐PMN preparations derived from 4 × 10 7 cells/ml stimulated culture 3 H‐thymidine incoporation to 3.56 ± 1.32 (SD) times controls levels. Although exposure of praparations to thiols reduced their mitogenicity, CTAP‐PMN was relatively heat‐stable. SDS gel eletrophoresis of active fractions suggested a molecular weight between 12,700 and 12, 700 daltons. In doulbe immunodiffusion, antisera to CTAP‐III showed no reactivity with CTAP‐PMN. CTAP‐PMN or other granulocyte factors capable of stimulating fibroblast DNA synthesis may play a role in chronic proliferative synovitis or in other settings where exudative inflammation is accompanied by connective tissue growth.