Activation of Human Synovial Cells by Cholera Enterotoxin: Correlation of Morphological Responses with Adenylate Cyclase Activities, and the Reversing Effects of Hyaluronidase

Abstract

Previously described morphological changes in human synovial cell cultures due to cholera enterotoxin (CT) were studied in relation to activation of adenylate cyclase. A single pulse of CT at nanomolar concentration or less induced at least two-fold activation of adenylate cyclase, which persisted for 7 days or more. The enzyme hyaluronidase was found to cause a rapid reversal of the morphological effects of CT. There was also a reduction in adenylate cyclase activity but only with hyaluronidase concentrations greater than those required to produce maximum reversal of the CT-induced morphological changes. Removal of hyaluronidase was followed by reappearance of the CT-associated morphological effects and a slower reactivation of adenylate cyclase. The mechanism by which hyaluronidase produces the observed changes in synovial cells is not known, but might be related to the dispersal of hyaluronic acid gels bound to the surface of these cells.