Fukushima C, Shimoda T, Matsuse H, Matsuo N, Takao A, Obase Y, Kohno S, Asai S
Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Ann Allergy Asthma Immunol. 1998 Mar;80(3):245-50. doi: 10.1016/S1081-1206(10)62965-1.
Chemical mediators induce bronchoconstriction, enhance vascular permeability, and promote inflammation. The use of synthetase inhibitors and receptor antagonists of these mediators may be useful in the treatment of asthma.
We evaluated the role of chemical mediators in mite antigen-induced contraction in resected human lung parenchyma using synthetase inhibitors and receptor antagonists for these mediators.
Resected human lung parenchymal specimens were passively sensitized with serum obtained from patients with asthma showing an IgE RAST score for mites > or = 5. The specimens were suspended in Magnus bath filled with buffer. After confirmation of contraction using PGF2 alpha, buffer or synthetase inhibitors or receptor antagonists of various chemical mediators were added. Contraction of parenchyma was induced by the addition of mite antigen, and the concentration of thromboxaneB2 (TXB2), leukotriene (LT), and histamine was measured before and after contraction.
Thromboxane A2 (TXA2) synthetase inhibitors significantly inhibited TXB2 release but not contraction. Leukotriene synthetase inhibitors significantly inhibited both LT release and contraction. The magnitude of the inhibitory effect was in the order of LT receptor antagonist > 5-lipoxygenase inhibitor > TXA2 receptor antagonist > PAF antagonist, TXA2 synthetase inhibitor, antihistamine > cyclooxygenase inhibitor.
Among chemical mediators, LT appears to be the most closely involved in the immediate antigen-induced contractile response in resected human lung parenchyma. Receptor antagonists produced a more marked inhibition of antigen-induced contraction than synthetase inhibitors.
化学介质可引起支气管收缩、增强血管通透性并促进炎症反应。使用这些介质的合成酶抑制剂和受体拮抗剂可能对哮喘治疗有用。
我们使用这些介质的合成酶抑制剂和受体拮抗剂，评估化学介质在切除的人肺实质中螨抗原诱导的收缩中的作用。
用从哮喘患者获得的血清对切除的人肺实质标本进行被动致敏，这些患者的螨IgE RAST评分≥5。将标本悬浮于装有缓冲液的马格努斯浴槽中。使用前列腺素F2α确认收缩后，加入缓冲液或各种化学介质的合成酶抑制剂或受体拮抗剂。加入螨抗原诱导实质收缩，并在收缩前后测量血栓素B2（TXB2）、白三烯（LT）和组胺的浓度。
血栓素A2（TXA2）合成酶抑制剂显著抑制TXB2释放，但不抑制收缩。白三烯合成酶抑制剂显著抑制LT释放和收缩。抑制作用的强度顺序为：LT受体拮抗剂＞5-脂氧合酶抑制剂＞TXA2受体拮抗剂＞血小板活化因子拮抗剂、TXA2合成酶抑制剂、抗组胺药＞环氧化酶抑制剂。
在化学介质中，LT似乎最密切参与切除的人肺实质中即刻抗原诱导的收缩反应。受体拮抗剂比合成酶抑制剂对抗原诱导的收缩产生更显著的抑制作用。
