Pulmonary intravascular macrophages and hemodynamic effects of liposomes in sheep.
Pulmonary intravascular macrophages and hemodynamic effects of liposomes in sheep.
复制标题
绵羊肺血管内巨噬细胞和脂质体的血流动力学效应。
DOI：
10.1152/jappl.1988.64.3.1143
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Staub,NC
中科院分区：
文献类型：
--
作者：
Miyamoto,K;Schultz,E;Heath,T;Mitchell,MD;Albertine,KH;Staub,NC
本文研究了脂质体对绵羊肺循环的影响，发现脂质体在肺内滞留与血管内巨噬细胞密切相关。静脉注射试验剂量的脂质体（5.5 μ mol总脂质）使肺动脉压从24± 2 cm H2O一过性升高至55 ± 16 cm H2O（SD）。肺动脉压反应具有剂量依赖性和可重复性。肺动脉压的升高被吲哚美辛完全阻断，血栓素合酶抑制剂阻断了75%。全身动脉血栓素B2浓度从低于50 pg/ml的基线水平升高至升压反应峰值时的250 ± 130 pg/ml。较大剂量的脂质体（220 μ mol的总脂质）静脉输注超过1小时增加肺动脉压最大限度地在第一个15分钟内。淋巴流量增加，淋巴蛋白浓度下降，提示静脉收缩。2 h后，半数以上（62.4 ± 15.7%）的111 In标记脂质体仍留在肺内。荧光和透射电子显微镜显示，超过90%的脂质体与肺泡壁微血管管腔中的单核细胞相关。我们的结论是脂质体影响肺动脉压短暂的机制，涉及花生四烯酸级联反应，主要是血栓素。我们的观察结果表明，一个人口的肺血管内巨噬细胞可能是血栓素和肺血流动力学和淋巴动力学的变化，发生在剂量依赖性的方式，虽然之间的相互作用脂质体，白细胞，或内皮细胞，除了巨噬细胞，尚未完全排除的来源。我们认为这是首次证明肺血管内巨噬细胞可能是花生四烯酸代谢物的来源，而不是内皮细胞、中性粒细胞或血管周围间质细胞。
We studied the effects of liposomes on the pulmonary circulation of sheep and found a close correlation between liposome retention in the lung and the intravascular macrophages. A test dose of liposomes (5.5 mumol of total lipids) injected intravenously transiently increased pulmonary arterial pressure from 24± 2 to 55 ± 16 (SD) cmH2O. The pulmonary arterial pressure responses were dose dependent and reproducible. The rise in pulmonary arterial pressure was blocked completely by indomethacin and 75% by a thromboxane synthase inhibitor. Systemic arterial thromboxane B2 concentration increased from a base-line level of less than 50 pg/ml to 250 ± 130 pg/ml at the peak of the pressor response. Larger doses of liposomes (220 mumol of total lipids) infused intravenously over 1 h increased pulmonary arterial pressure maximally within the first 15 min. Lymph flow increased and lymph protein concentration decreased, suggesting venoconstriction. Over half (62.4 ± 15.7%) of 111In-labeled liposomes remained in the lung after 2 h. Fluorescence and transmission electron microscopy showed that greater than 90% of the liposomes were associated with mononuclear cells in the lumen of the alveolar wall microvessels. We conclude that liposomes affect pulmonary arterial pressure transiently by a mechanism involving the arachidonate cascade, principally thromboxane. Our observations suggest that a population of pulmonary intravascular macrophages is likely to be the source of the thromboxane and the pulmonary hemodynamic and lymph dynamic changes that occur in a dose-dependent fashion, although interactions between liposomes, leukocytes, or endothelial cells, in addition to the macrophages, have not been completely ruled out. We believe this is the first demonstration that pulmonary intravascular macrophages may be the source of the arachidonate metabolites rather than endothelial cells, neutrophils, or perivascular interstitial cells.