Tumor necrosis factor α (TNFα) stimulated rapid (seconds) hydrolysis of sphingomyelin in HL-60 cells, formation of phosphocholine (PCho) and a decrease in choline. The response to TNFα was concentration dependent with a maximal effect at 3-10 nM. The monoclonal antibody (mAb). htr-9, which behaves as an agonist at the 55 kDa subtype of the TNF receptor, also stimulated sphingomyelin hydrolysis in intact cells. In contrast, the mAb, utr-1, which behaves as an antagonist at the 75 kDa receptor subtype, had no effect on sphingomyelin hydrolysis either on its own or in the presence of TNFα. In addition, htr-9 or TNFα stimulated hydrolysis of sphingomyelin in a membrane fraction of HL-60 cells. These results are consistent with a role of sphinpomyelin hydrolysis as an early event in the signalling mechanism or TNFα, and suggest that this pathway is activated through the 55 kDa subtype of the TNF receptor.
All Science Journal Classification (ASJC) codes
- Structural Biology
- Molecular Biology
- Cell Biology