Saturable, high affinity binding of serum amyloid A (SAA₃) to rabbit fibroblasts

Abstract

Rabbit serum amyloid A (SAA₃; 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 SAA₃ binds to monolayers of synovial fibroblasts. Using ¹²⁵I-SAA, we demonstrate that SAA₃ binds to rabbit fibroblasts with characteristics consistent with the existence of cellular receptors. Binding is specific and satarable, with an affinity of about 20 nM and approximately 800,000 sites/cell. Cross-linking studies with ¹²⁵I-SAA reveal cross-linked proteins of 92, 72 and 53 kDA. Over time, there is a decrease in amount of¹²⁵I-SAA binding to cells, perhaps due to internalization/down regulation of receptors and/or some degradation of the ligand. We conclude that rabbit SAA₃ 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.

Key Words:

• INFLAMMATION
• CONNECTIVE TISSUE
• RECEPTOR
• COLLAGENASE