Department of Disaster Psychiatry, International Research Institute for Disaster Science, Tohoku University.
Department of Tumor Biology, Institute of Biomedical Sciences, Iwate Medical University.
Biol Pharm Bull. 2019;42(8):1253-1267. doi: 10.1248/bpb.b18-00975.
Systemic platelet behaviors in experimental animals are often assessed by infusion of isotope-labeled platelets and measuring them under anesthesia. However, such procedures alter, therefore may not reveal, real-life platelet behaviors. 5-Hydroxytryptamine (5HT or serotonin) is present within limited cell-types, including platelets. In our studies, by measuring 5HT as a platelet-marker in non-anesthetized mice, we identified stimulation- and time-dependent accumulations in liver, lung, and/or spleen as important systemic platelet behaviors. For example, intravenous, intraperitoneal, or intragingival injection of lipopolysaccharide (LPS, a cell-wall component of Gram-negative bacteria), interleukin (IL)-1, or tumor necrosis factor (TNF)-α induced hepatic platelet accumulation (HPA) and platelet translocation into the sinusoidal and perisinusoidal spaces or hepatocytes themselves. These events occurred "within a few hours" of the injection, caused hypoglycemia, and exhibited protective or causal effects on hepatitis. Intravenous injection of larger doses of LPS into normal mice, or intravenous antigen-challenge to sensitized mice, induced pulmonary platelet accumulation (PPA), as well as HPA. These reactions occurred "within a few min" of the LPS injection or antigen challenge and resulted in shock. Intravenous injection of 5HT or a catecholamine induced a rapid PPA "within 6 s." Intravenous LPS injection, within a minute, increased the pulmonary catecholamines that mediate the LPS-induced PPA. Macrophage-depletion from liver and spleen induced "day-scale" splenic platelet accumulation, suggesting the spleen is involved in clearing senescent platelets. These findings indicate the usefulness of 5HT as a marker of platelet behaviors, and provide a basis for a discussion of the roles of platelets as both "defenders" and "guardians."
在实验动物中，通常通过输注同位素标记的血小板并在麻醉下测量来评估系统性血小板行为。然而，这些程序会改变，因此可能无法揭示真实的血小板行为。5-羟色胺（5HT 或血清素）存在于包括血小板在内的有限细胞类型中。在我们的研究中，通过在非麻醉小鼠中测量 5HT 作为血小板标志物，我们发现刺激和时间依赖性的肝、肺和/或脾中的血小板积聚是重要的系统性血小板行为。例如，静脉内、腹腔内或牙龈内注射脂多糖（LPS，革兰氏阴性菌细胞壁的组成部分）、白细胞介素（IL）-1 或肿瘤坏死因子（TNF）-α 会诱导肝血小板积聚（HPA）和血小板转移到窦状隙和窦周间隙或肝细胞本身。这些事件发生在注射后的“几个小时内”，导致低血糖，并对肝炎具有保护或因果作用。向正常小鼠静脉内注射较大剂量的 LPS 或向致敏小鼠静脉内抗原挑战，会诱导肺血小板积聚（PPA）和 HPA。这些反应发生在 LPS 注射或抗原挑战后的“几分钟内”，并导致休克。静脉内注射 5HT 或儿茶酚胺会导致快速的 PPA“在 6 秒内发生”。静脉内 LPS 注射在一分钟内增加了介导 LPS 诱导的 PPA 的肺儿茶酚胺。从肝和脾中耗尽巨噬细胞会诱导“天级”的脾血小板积聚，表明脾脏参与清除衰老的血小板。这些发现表明 5HT 作为血小板行为标志物的有用性，并为讨论血小板作为“防御者”和“守护者”的作用提供了基础。
