血管内皮細胞の凝固・線溶因子発現に対するCD40-CD40 Ligand (CD40L) 相互作用の影響を検討する目的で, 培養血管内皮細胞とCD40L発現リンパ球の接着実験を行った. IFN-γで活性化し, CD40発現を増加させた血管内皮細胞と, CD40Lを発現させた後固定したTリンパ球を共培養すると, 血管内皮細胞表面に tissue factor (TF) の強い発現が認められた. このTF発現は抗CD40L抗体で, 部分的ではあるが特異的に阻害された. また, CD40L発現Tリンパ球の接着により, 血管内皮細胞中の thrombomodulin 抗原量および培養上清中の tissue factor pathway inhibitor 抗原量は低下した. 一方, 血管内皮細胞による tissue-type plasminogen activator の産生・放出は著しく増加したが, 培養上清中には plasminogen activator inhihibitor-1が常に過剰量存在していた. 以上のことから, 炎症性免疫反応部位において血管内皮細胞に活性化Tリンパ球が接着すると, 血管内皮細胞表面は凝固亢進状態へ著しく modulate されるという結論が得られた. なお, この反応にはCD40-CD40L相互作用の関与が示唆された.

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A 9 years old Japanese non-albino girl has presented with mild to moderate nosebleed. Routine studies revealed normal counts and sizes of the patient's platelets and normal coagulation tests but prolonged bleeding times (over 12min). The platelets showed normal shape change in response to ADP. Aggregations of the platelets by ADP and collagen were significantly delayed in onset and weaker than controls, while aggregation/agglutination by epinephrine, thrombin, A23187 or ristocetin were normal, suggesting that the patient's platelets are abnormal only in ADP-induced activation. The platelet ATP secretion by 20μg/ml collagen was about half of controls by a Lumi-aggregometer. ³H-ADP binding to the patient's platelets as well as Ca²⁺ influx and mobilization induced by ADP were normal, suggesting a normal quantity of three ADP receptors and a normal function of P2X₁, a component of the receptors. Immunoblots revealed that Giα subunit, a G-protein associated with P2Yac that is the second component of the receptors, was decreased in the patient's platelets than controls, but Gqα subunit, a G-protein associated with P2Y₁ that is the third component of the receptors, was normal in the patient's platelets. Stimulation of PGE₁-pretreated platelets by 10μM ADP or 10μM epinephrine reduced the cAMP levels in the patient's platelets to the same extent as in control platelets, indicating a normal function of P2Yac in spite of the decreased Giα subunit. The patient's platelet abnormality characterized with defective activation induced by ADP appears to originate from defective coordination between decreased Giαsubunit and other ADP receptors.

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