SATURABLE, HIGH-AFFINITY BINDING OF SERUM AMYLOID-A (SAA(3)) TO RABBIT FIBROBLASTS

Rabbit serum amyloid A (SAA(3); Mr 14 kDa) is a novel form of SAA that is produced by rabbit synovial fibroblasts and that acts as an autocrine factor in these cells to induce production of collagenase (matrix metalloproteinase-1). In this study, we investigated the mechanism by which SAA(3) binds to monolayers of synovial fibroblasts. Using I-125-SAA, we demonstrate that SAA(3) binds to rabbit fibroblasts with characteristics consistent with the existence of cellular receptors. Binding is specific and saturable, with an affinity of about 20 nM and approximately 800, 000 sites/cell. Cross-linking studies with I-125-SAA reveal cross-linked proteins of 92, 72 and 53 kDA. Over time, there is a decrease in amount of I-125-SAA binding to cells, perhaps due to internalization/down regulation of receptors and/or some degradation of the ligand. We conclude that rabbit SAA(3) is one of several proteins that stimulates collagenase synthesis via specific cellular receptors, and we suggest that this redundancy in inductive pathways may provide a variety of mechanisms for regulating collagenase gene expression.