Cyclooxygenase inhibition during phorbol-induced granulocyte stimulation in awake sheep.
Cyclooxygenase inhibition during phorbol-induced granulocyte stimulation in awake sheep.
复制标题
在佛波醇诱导的清醒羊粒细胞刺激过程中环加氧酶的抑制。
DOI：
10.1152/jappl.1984.56.4.999
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Brigham,KL
中科院分区：
文献类型：
--
作者：
Newman,JH;Loyd,JE;Ogletree,ML;Meyrick,BO;Brigham,KL
在体外，佛波醇肉豆蔻酸酯乙酸酯（PMA）导致绵羊粒细胞释放超氧化物。注入绵羊体内，PMA会导致白细胞减少、低氧血症、肺动脉高压和富含蛋白质的肺淋巴液流量增加。肺淋巴血栓素B2和6-酮前列腺素F1 α水平在PMA输注后显著升高。为了观察花生四烯酸的环氧合酶产物是否介导肺血管对PMA的反应，我们在6只绵羊中分别输注了两次5 μ g/kg PMA，一次是在存在甲氨蝶呤钠的情况下，一次是单独输注。我们改变了配对实验的顺序，并允许实验之间间隔4-7天。甲氨蝶呤（5 mg/kg负荷剂量+ 3 mg X kg-1 X h-1输注）单独给药对基线变量无影响。甲氨蝶呤抑制或延迟PMA后的初始肺动脉高压和低氧血症，但加剧了随后的肺动脉压升高;它阻止了PMA后血栓素B2和6-酮前列腺素F1 α的任何升高。甲氨蝶呤不影响白细胞减少症的程度或后期低氧血症的严重程度，也不阻止粒细胞在肺中蓄积。与PMA单独给药相比，Meclutamate + PMA组肺淋巴流量增加，但淋巴细胞与血浆蛋白浓度比值降低，表明Meclutamate对PMA后淋巴细胞生成的主要影响与肺动脉高压程度有关。我们的结论是，PMA引起的肺动脉压的早期增加是由花生四烯酸的环氧合酶产物介导的，可能是血栓素A2，但后来的肺动脉高压和肺血管通透性的增加不是环氧合酶产物的结果。
In vitro, phorbol myristate acetate (PMA) causes sheep granulocytes to release superoxide. Infused into sheep, PMA causes leukopenia, hypoxemia, pulmonary hypertension, and increased flow of protein-rich lung lymph. Lung lymph thromboxane B2 and 6-ketoprostaglandin F1 alpha levels rise markedly after PMA infusion. To see whether cyclooxygenase products of arachidonic acid mediate the lung vascular responses to PMA, we infused 5 micrograms/kg PMA twice in each of six sheep, once in the presence of sodium meclofenamate and once alone. We varied the order of paired experiments and allowed 4–7 days between experiments. Meclofenamate (5 mg/kg loading dose + 3 mg X kg-1 X h-1 infusion) given alone had no effect on base-line variables. Meclofenamate inhibited or delayed the initial pulmonary hypertension and hypoxemia after PMA but exaggerated the later increase in pulmonary arterial pressure; it prevented any increase in thromboxane B2 and 6-ketoprostaglandin F1 alpha after PMA. Meclofenamate did not affect the degree of leukopenia or the severity of the later hypoxemia nor did it prevent accumulation of granulocytes in the lung. Lung lymph flow was higher with meclofenamate + PMA than with PMA alone, but lymph-to-plasma protein concentration ratio was lower, suggesting that the main effect of meclofenamate on lymph production after PMA was related to the degree of pulmonary hypertension. We conclude that the early increase in pulmonary arterial pressure caused by PMA is mediated by a cyclooxygenase product of arachidonic acid, possibly thromboxane A2, but the later pulmonary hypertension and the increase in pulmonary vascular permeability are not the result of cyclooxygenase products.