Ishiguro Kyoko, Oku Hisae, Ueda Yoshimi, Iwaoka Emiko, Kunitomo Masaru
School of Pharmaceutical Sciences, Mukogawa Women's University, Koshien Kyuban-cho, Nishinomiya, Hyogo 663-8179, Japan.
Biol Pharm Bull. 2005 Aug;28(8):1490-5. doi: 10.1248/bpb.28.1490.
We discovered a phenomenon in which the blood flow in vein microcirculation markedly decreases in response to hen-egg white lysozyme (HEL)-sensitization without any change in blood pressure. Using this blood flow decrease as a guide, we developed an in vivo assay method to search for substances, which can prevent allergies. Antagonists of histamine, serotonin and platelet activating factor (PAF) did not affect the blood flow decrease in response to HEL-sensitization. On the other hand, cyclooxygenase (COX)-1, COX-2, thromboxane (TX) A(2), endothelin-1 (ET-1), prostacyclin (PGI(2)) and granulocytic elastase (GE) as well as nitric oxide (NO) from inducible NO synthase (iNOS) were involved in the blood flow decrease. Thus, these substances might injure vascular endothelial cells, and cause a decrease in blood flow in vein microcirculation. Our method can be used to search for preventive agents against allergies involving NO, COX-1, 2 and PGI(2). This is the first report to applying to an assay method the specific blood flow decrease to occur in the promotion stage of allergy.
我们发现了一种现象，即蛋清溶菌酶（HEL）致敏后静脉微循环中的血流显著减少，而血压无任何变化。以这种血流减少为指导，我们开发了一种体内检测方法来寻找可预防过敏的物质。组胺、5-羟色胺和血小板活化因子（PAF）的拮抗剂对HEL致敏引起的血流减少没有影响。另一方面，环氧化酶（COX）-1、COX-2、血栓素（TX）A2、内皮素-1（ET-1）、前列环素（PGI2）、粒细胞弹性蛋白酶（GE）以及诱导型一氧化氮合酶（iNOS）产生的一氧化氮（NO）都与血流减少有关。因此，这些物质可能会损伤血管内皮细胞，并导致静脉微循环中的血流减少。我们的方法可用于寻找针对涉及NO、COX-1、2和PGI2的过敏的预防剂。这是首次将过敏促进阶段发生的特定血流减少应用于检测方法的报告。
