三磷酸腺苷（ATP）调节抗免疫球蛋白E（anti-IgE）诱导的人肺肥大细胞组胺释放。

ATP modulates anti-IgE-induced release of histamine from human lung mast cells.

作者信息

Schulman E S, Glaum M C, Post T, Wang Y, Raible D G, Mohanty J, Butterfield J H, Pelleg A

机构信息

Divisions of Pulmonary/Critical Care and Cardiology, Department of Medicine, Medical College of Pennsylvania/Hahnemann School of Medicine, Philadelphia, Pennsylvania 19102-1192, USA.

出版信息

Am J Respir Cell Mol Biol. 1999 Mar;20(3):530-7. doi: 10.1165/ajrcmb.20.3.3387.

DOI:10.1165/ajrcmb.20.3.3387

PMID:10030852

Abstract

Adenosine 5'-triphosphate (ATP) is released from the cytoplasm under physiologic and pathophysiologic conditions and enters the extracellular space, where it acts on a group of recently cloned cell-surface receptors termed P2-purinoceptors (subtypes P2X and P2Y). We examined the effects of extracellular ATP, uridine triphosphate (UTP), the stable ATP analogues alpha,betamethylene-ATP (alpha,betamATP), beta,gammamethylene-ATP (beta,gammamATP), and 2-methylthio-ATP (2mSATP), and adenosine (10(-6)-10(-3) M) on histamine release from human lung mast cells (HLMC) induced by anti-IgE and the calcium ionophore A23187. None of the nucleotides or adenosine directly induced histamine release. Adenosine exhibited a bimodal effect, enhancing histamine release at 10(-6) to 10(-4) M (P > 0.05, NS) and inhibiting it at 10(-3) M (P < 0.05). ATP (10(-4) M) enhanced anti-IgE-induced histamine release (10.9 +/- 2.7% to 19. 2 +/- 2.9%, n = 20, P < 0.01), but not ionophore A23187-induced histamine release (n = 10). The adenine nucleotides consistently enhanced anti-IgE-induced histamine release; the rank order for this action was: ATP > 2mSATP > alpha,betamATP > beta,gammamATP, suggesting mediation by a P2Y-purinoceptor subtype. The selective P2X purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2', 4'-disulfonic acid failed to influence the effect of ATP, further supporting P2Y-purinoceptor mediation of anti-IgE-induced histamine release. UTP, an agonist at P2Y-purinoceptors, also significantly enhanced anti-IgE-induced histamine release. Application of the reverse transcription-polymerase chain reaction indicated that HLMC constitutively express the messenger RNAs encoding the P2Y1- and P2Y2-purinoceptor subtypes, and not that encoding the P2X7-purinoceptor (i.e., P2Z), a subtype implicated in ATP-induced histamine release in rodent peritoneal mast cells. The data produced in the study suggest that ATP plays an important modulatory role in histamine release from HLMC, and that it may therefore be mechanistically involved in human allergic/asthmatic reactions.

摘要

在生理和病理生理条件下，腺苷5'-三磷酸（ATP）从细胞质中释放出来并进入细胞外空间，在那里它作用于一组最近克隆的细胞表面受体，称为P2-嘌呤受体（P2X和P2Y亚型）。我们研究了细胞外ATP、尿苷三磷酸（UTP）、稳定的ATP类似物α,β-亚甲基-ATP（α,βmATP）、β,γ-亚甲基-ATP（β,γmATP）和2-甲硫基-ATP（2mSATP）以及腺苷（10⁻⁶ - 10⁻³ M）对由抗IgE和钙离子载体A23187诱导的人肺肥大细胞（HLMC）组胺释放的影响。这些核苷酸或腺苷均未直接诱导组胺释放。腺苷表现出双峰效应，在10⁻⁶至10⁻⁴ M时增强组胺释放（P > 0.05，无显著性差异），而在10⁻³ M时抑制组胺释放（P < 0.05）。ATP（10⁻⁴ M）增强了抗IgE诱导的组胺释放（从10.9 ± 2.7%增至19.2 ± 2.9%，n = 20，P < 0.01），但未增强离子载体A23187诱导的组胺释放（n = 10）。腺嘌呤核苷酸始终增强抗IgE诱导的组胺释放；此作用的强度顺序为：ATP > 2mSATP > α,βmATP > β,γmATP，提示由P2Y-嘌呤受体亚型介导。选择性P2X嘌呤受体拮抗剂磷酸吡哆醛-6-偶氮苯基-2',4'-二磺酸未能影响ATP的作用，进一步支持抗IgE诱导的组胺释放由P2Y-嘌呤受体介导。UTP是P2Y-嘌呤受体的激动剂，也显著增强了抗IgE诱导的组胺释放。逆转录-聚合酶链反应的应用表明，HLMC组成性表达编码P2Y1和P2Y2-嘌呤受体亚型的信使RNA，而不表达编码P2X7-嘌呤受体（即P2Z）的信使RNA，P2X7-嘌呤受体是一种与啮齿动物腹膜肥大细胞中ATP诱导的组胺释放有关的亚型。该研究所得数据表明，ATP在HLMC组胺释放中起重要调节作用，因此可能在人类过敏/哮喘反应的机制中发挥作用。