ACETYLCHOLINESTERASE ACTIVATION OF PERITONEAL-MACROPHAGES IS INDEPENDENT OF CATALYTIC ACTIVITY

1. In diverse tissues, acetylcholinesterase appears to play a critical role in the functional state of cells completely dependent of choline rgic transmission. However, very little is known about the mechanisms and actual molecular structures mediating the fundamental interactions between this protein and the cellular membrane. 2. In this study, per itoneal macrophages were used as a model system to study the possible interaction between acetylcholinesterase, acting in a noncholinergic c apacity, and the cellular membrane. 3. When acetylcholinesterase was i ncubated with macrophages harvested from rat peritoneum, the rate of o xygen consumption was increased in a concentration-dependent manner th at was independent of mitochondrial block with sodium cyanide. Further more, heat inactivation of enzymatic activity or application of BW 284 C51 at a concentration which totally blocks catalytic activity did not eliminate the effect. 4. In contrast, incubation with bovine serum al bumin or butyrylcholinesterase actually retarded oxygen consumption. 5 . The effect of acetylcholinesterase depended on the presence of dival ent cations and was inhibited by mannan and D-mannose, but not D-galac tose. It is concluded that acetylcholinesterase can induce a ''respira tory burst'' in macrophages independent of its conventional catalytic site but involving either the mannose receptor of the monocyte-derived macrophage binding site on acetylcholinesterase itself.