腫瘍壊死因子による直接的肺血管内皮細胞傷害に血小板活性化因子は関与しない

Platelet Activating Factor Does not Participate in Direct Endothelial Cell Injury Caused by Tumor Necrosis Factor

　腫瘍壊死因子（TNF）による直接的肺血管内皮細胞傷害に対する血小板活性化因子（PAF）の関与を検討した．ウシ肺動脈内皮細胞を⁵¹Crで標識した．PAF受容体拮抗剤であるTCV−309（10⁻⁹〜10⁻⁵M）をTNF投与30分前に添加した．各濃度のTNFを培養液に添加し18時間培養した．培養後上清中への⁵¹Cr放出率を求め，血管内皮細胞傷害の指標とした．TNF1U／ml以上で内皮細胞傷害を認めた．TCV−309は検討した全濃度でTNFによる内皮細胞傷害を抑制しなかった．PAFはTNFによる内皮細胞傷害に関与しないと考えた．

Platelet activating factor (PAF) is a lipid mediator of inflammation produced by a variety of cells. Endoth-elial 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 endoth-elial 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^-5M) was ad-ministered 30 minutes before TNF 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 1U/ml was capable of causing endothelial cell injury. TCV-309 at all concentrations used, failed to attenuate the endothelial cell injury caused by TNF 1 U/ml. PAF does not appear to participate in direct endothelial cell injury caused by TNF.