组胺在生理和免疫刺激引起的血小板聚集过程中的作用。

The role of histamine in platelet aggregation by physiological and immunological stimuli.

作者信息

Masini E, Di Bello M G, Raspanti S, Ndisang J F, Baronti R, Cappugi P, Mannaioni P F

机构信息

Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.

出版信息

Inflamm Res. 1998 May;47(5):211-20. doi: 10.1007/s000110050319.

DOI:10.1007/s000110050319

PMID:9657253

Abstract

BACKGROUND

Platelets participate in allergic and inflammatory processes beside their role in haemostasis and thrombosis. This paper reports the level, the uptake, the metabolism and the release of histamine in human platelets. The effects of exogenous histamine, as well as the receptor and signal transduction of these effects, are also described.

METHODS

Purified suspensions of platelets, prepared from healthy volunteers and from atopic patients, were exposed in vitro to physiological and immunological stimuli. Platelet aggregation was measured by the increase in light transmission; histamine content and release, as well as cytosolic free Ca2+ concentration, were measured fluorimetrically. Platelet histamine forming capacity, and the uptake of exogenous histamine, were measured with a radioisotopic method.

RESULTS

Human platelets contain 72.5 +/- 9.6pmoles of histamine x 10(9) platelets, and their capacity to form histamine is 18.7 +/- 3.5pmoles h(-1)g(-1) protein, which is reduced by alpha-fluoromethylhistidine (10(-5) M) a selective inhibitor of the specific histidine decarboxylase. Human platelets take up the preformed amine by a calcium and energy-dependent process, and the uptake of histamine is reduced by mepyramine, an H1-receptor antagonist, and N,N-diethyl-2-[4-(phenylmethyl) phenoxyl] ethanamine (10(-6) M), a blocker of intracellular histamine receptors. Histamine is also metabolized by human platelets. The exposure of platelets to thrombin (10-60 mUml(-1)) produced a progressive aggregation, associated with histamine release. The same is observed in platelets isolated from atopic patients exposed to anti-IgE antibodies. Exogenous histamine dose-dependently potentiates the aggregation induced by physiological and immunological stimuli. In resting platelets cytosolic calcium level (207 +/- 4.2 nM/10(8) platelets) is increased by thrombin as well as by anti-IgE; this effect is potentiated by 10(-5) M histamine.

CONCLUSIONS

The synergistic effect between histamine and other monoamines on platelet aggregation may explain some aspects of allergic vasculitis in which platelet aggregation is present.

摘要

背景

血小板除了在止血和血栓形成中发挥作用外，还参与过敏和炎症过程。本文报道了人血小板中组胺的水平、摄取、代谢和释放情况。还描述了外源性组胺的作用及其受体和信号转导。

方法

从健康志愿者和特应性患者制备的纯化血小板悬液，在体外暴露于生理和免疫刺激。通过光透射增加来测量血小板聚集；用荧光法测量组胺含量、释放以及胞质游离钙离子浓度。用放射性同位素方法测量血小板组胺形成能力和外源性组胺的摄取。

结果

人血小板含有72.5±9.6皮摩尔组胺×10⁹个血小板，其组胺形成能力为18.7±3.5皮摩尔·小时⁻¹·克⁻¹蛋白质，该能力可被特异性组氨酸脱羧酶的选择性抑制剂α-氟甲基组胺（10⁻⁵M）降低。人血小板通过钙和能量依赖过程摄取预先形成的胺，组胺的摄取可被H1受体拮抗剂美吡拉敏和细胞内组胺受体阻滞剂N,N-二乙基-2-[4-(苄基)苯氧基]乙胺（10⁻⁶M）降低。组胺也可被人血小板代谢。血小板暴露于凝血酶（10 - 60 mU/ml⁻¹）会产生逐渐的聚集，并伴有组胺释放。在暴露于抗IgE抗体的特应性患者分离的血小板中也观察到同样情况。外源性组胺剂量依赖性地增强生理和免疫刺激诱导的聚集。在静息血小板中，凝血酶和抗IgE均可使胞质钙水平（207±4.2 nM/10⁸个血小板）升高；10⁻⁵M组胺可增强此效应。