Platelet activating factor does not participate in direct endothelial cell injury caused by tumor necrosis factor

Platelet activating factor (PAF) is a lipid mediator of inflammation produced by a variety of cells. Endothelial cells synthesize PAF in response to various stimuli and PAF remains cell-associated. This study was designed to elucidate whether PAF participates in direct endothelial cell injury caused by tumor necrosis factor (TNF). Bovine pulmonary artery endothelial cells (BPAEC) were labelled with ⁵¹Cr to detect endothelial cell injury. Various concentrations of TNF were added to culture media and BPAEC were incubated for 18 hours. Controls were treated with only culture medium. To investigate the role of PAF, the PAF receptor antagonist TCV-309 (10^-9~10^-5 M) was administered 30 minutes before TMF administration. After incubation, the medium was collected and ⁵¹Cr activity was measured. %Release of ⁵¹Cr into the medium was calculated and an increase was considered to be due to endothelial cell injury. TNF more than 1 U/ml was capable of causing endothelial cell injury. TCV-309 at all concentrations used, failed to attenuated the endothelial cell injury caused by TNF 1 U/ml. PAF does not appear to participate in direct endothelial cell injury caused by TNF.