Neutrophil Aggregation: Evidence for a Different Mechanism of Action by Phorbol Myristate Acetate

AbstractChemotactic factors, the ionophore A23187, and arachidonic acid aggregate polymorphonuclear neutrophils. They appear to act in part by causing neutrophils to take up extracellular calcium and to metabolize arachidonic acid. Hence, the aggregation response to these stimuli requires extracellular calcium, is enhanced by cytochalasin B (which enhances calcium uptake in stimulated cells), and is inhibited by arachidonate antimetabolites. Here, phorbol myristate acetate was also found to aggregate neutrophils. However, this response was relatively insensitive to extracellular calcium, cytochalasin B, and arachidonate antimetabolites. The mechanism of action of the phorbol ester, therefore, may not require calcium influx nor arachidonate metabolism. This suggests that neutrophil aggregation can occur through at least two different mechanisms. Other neutrophil responses (e.g., release of specific granule enzymes and oxidative metabolism) may also proceed through these same mechanisms. Phorbol myristate a...