Forsythe P, McGarvey L P, Heaney L G, MacMahon J, Ennis M
Department of Clinical Biochemistry, Institute of Clinical Science, The Queen's University of Belfast, Grosvenor Road, Belfast BT12 6BJ, U.K.
Clin Sci (Lond). 1999 Apr;96(4):349-55.
Previous studies have shown that in vitro adenosine enhances histamine release from activated human lung mast cells obtained by enzymic dispersion of lung parenchyma. However, adenosine alone has no effect on histamine release from these cells. Given the evidence for direct activation of mast cells after endobronchial challenge with adenosine and previous studies indicating that mast cells obtained at bronchoalveolar lavage are a better model for asthma studies than those obtained by enzymic dispersion of lung tissue, the histamine-releasing effect of adenosine was examined on lavage mast cells. Bronchoalveolar lavage fluid was obtained from patients attending hospital for routine bronchoscopy (n=54). Lavage cells were challenged with adenosine or adenosine receptor agonists (20 min, 37 degrees C) and histamine release determined using an automated fluorometric assay. Endogenous adenosine levels were also measured in lavage fluid (n=9) via an HPLC method. Adenosine alone caused histamine release from lavage mast cells in 37 of 54 patients with a maximal histamine release of 20.56+/-2.52% (range 5.2-61%). The adenosine receptor agonists (R)-N6-(2-phenylisopropyl)adenosine, 5'-N-ethylcarboxamidoadenosine and CGS21680 also induced histamine release from lavage mast cells. Preincubation of lavage mast cells with the adenosine receptor antagonist xanthine amine congener caused significant inhibition of the response to adenosine (P=0.007). There was an inverse correlation between endogenous adenosine levels in the lavage fluid and the maximal response to in vitro adenosine challenge of the lavage cells. The findings of the present study indicate a means by which adenosine challenge of the airways can induce bronchoconstriction and support a role for adenosine in the pathophysiology of asthma. The results also suggest that cells obtained from bronchoalveolar lavage fluid may provide the ideal model for the testing of novel, adenosine receptor, targeted therapies for asthma.
先前的研究表明，体外实验中，腺苷可增强通过酶分散肺实质获得的活化人肺肥大细胞的组胺释放。然而，单独的腺苷对这些细胞的组胺释放没有影响。鉴于支气管内给予腺苷后肥大细胞被直接激活的证据，以及先前的研究表明，支气管肺泡灌洗获得的肥大细胞比通过酶分散肺组织获得的肥大细胞更适合作为哮喘研究的模型，因此研究了腺苷对灌洗肥大细胞的组胺释放作用。从因常规支气管镜检查入院的患者（n = 54）中获取支气管肺泡灌洗液。用腺苷或腺苷受体激动剂刺激灌洗细胞（37℃，20分钟），并使用自动荧光测定法测定组胺释放。还通过高效液相色谱法测量灌洗液中的内源性腺苷水平（n = 9）。在54例患者中，单独的腺苷导致37例灌洗肥大细胞释放组胺，组胺最大释放量为20.56±2.52%（范围5.2 - 61%）。腺苷受体激动剂（R）-N6-（2-苯异丙基）腺苷、5'-N-乙基羧酰胺腺苷和CGS21680也诱导灌洗肥大细胞释放组胺。用腺苷受体拮抗剂黄嘌呤胺同类物预孵育灌洗肥大细胞可显著抑制对腺苷的反应（P = 0.007）。灌洗液中的内源性腺苷水平与灌洗细胞对体外腺苷刺激的最大反应呈负相关。本研究结果表明，气道给予腺苷可诱导支气管收缩的一种方式，并支持腺苷在哮喘病理生理学中的作用。结果还表明，从支气管肺泡灌洗液中获得的细胞可能为测试新型腺苷受体靶向哮喘治疗提供理想模型。
