MONONUCLEAR-CELLS FROM DOGS WITH ACUTE LUNG ALLOGRAFT-REJECTION CAUSE CONTRACTION OF PULMONARY-ARTERIES

MONONUCLEAR-CELLS FROM DOGS WITH ACUTE LUNG ALLOGRAFT-REJECTION CAUSE CONTRACTION OF PULMONARY-ARTERIES
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DOI:
10.1161/01.cir.90.2.952
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发表时间:
1994-08-01
期刊:
影响因子:
37.8
通讯作者:
MILLER, VM
MILLER, VM
中科院分区:
医学1区
文献类型:
--
作者:
CALE, ARJ;RICAGNA, F;MILLER, VM

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目的探讨急性肺排斥反应激活的白细胞是否引起离体肺动脉收缩。方法和结果分离(a)多形核细胞(>95%)和(B)单个核细胞悬液(85%淋巴细胞/10%单核细胞/5%多形核细胞)分别从四组成年雄性杂种犬的动脉血中获得:未手术的狗(对照)、单肺自体移植的狗、排斥单肺同种异体移植的狗和用与同种异体移植的狗相同的免疫抑制剂治疗的未手术的狗。将这些悬浮液加入到悬浮在器官腔室中的对照叶内肺动脉环中以测量等长力。从选定的环上机械去除内皮。添加四组狗中任何一组的多形核细胞悬液后,肺动脉环的基础张力均未发生显着变化。未手术犬、自体移植犬和未手术、用药犬的单核细胞悬液张力显著增加,且细胞数量依赖性。与没有内皮的那些相比,这些张力的增加在环中较少。添加L-精氨酸的合成类似物消除了这种差异。与未手术的自体移植犬或未手术的药物治疗犬的悬浮细胞相比,来自排斥同种异体移植犬的单核细胞悬浮液引起内皮环显著更大的收缩。此外,超氧化物歧化酶加过氧化氢酶或内皮素-A受体(BQ-123)的拮抗剂减少收缩环内皮细胞,但不是在那些没有内皮细胞的排斥allotransplanted犬的单核细胞悬液。结论这项研究的结果表明,单核细胞引起肺动脉收缩,这可以部分抑制内皮源性一氧化氮。然而,如果单核细胞被急性肺排斥反应激活,收缩不再被内皮抑制。在排斥反应条件下,收缩部分由氧自由基和内皮素介导。
Purpose Experiments were designed to determine whether or not leukocytes activated by acute pulmonary rejection cause contractions of isolated pulmonary arteries.Methods and Results Separate suspensions of (a) polymorphonuclear cells (>95%) and (b) mononuclear cells (85% lymphocytes/10% monocytes/5% polymorphonuclear cells), respectively, were obtained from the arterial blood of four groups of adult male mongrel dogs: unoperated dogs (controls), dogs with single-lung autotransplants, dogs with rejecting single-lung allotransplants, and unoperated dogs treated with the same immunosuppressants as allotransplanted dogs. These suspensions were added to rings of control intralobar pulmonary arteries suspended in organ chambers for measurement of isometric force. The endothelium was removed mechanically from selected rings. No significant change in basal tension of pulmonary arterial rings occurred by adding suspensions of polymorphonuclear cells from any of the four groups of dogs. Significant cell-number-dependent increases in tension occurred with suspensions of mononuclear cells from unoperated dogs, autotransplanted dogs, and unoperated, medicated dogs. These increases in tension were less in rings with compared to those without endothelium. Addition of a synthetic analogue of L-arginine abolished this difference. Suspensions of mononuclear cells from rejecting allotransplanted dogs caused significantly greater contractions in rings with endothelium than those observed with suspended cells from either unoperated, autotransplanted dogs or unoperated, medicated dogs. Addition of superoxide dismutase plus catalase or an antagonist of endothelin-A receptors (BQ-123) reduced contractions in rings with endothelium but not in those without endothelium to suspensions of mononuclear cells from rejecting allotransplanted dogs.Conclusions The results of this study suggest that mononuclear cells cause contraction of pulmonary arteries, which can be partially inhibited by endothelium-derived nitric oxide. However, if the mononuclear cells are activated by acute pulmonary rejection, contractions are no longer inhibited by the endothelium. Under conditions of rejection, contractions are mediated in part by oxygen radicals and endothelin(s).