Cohler L F, Saba T M, Lewis E, Vincent P A, Charash W E
Department of Physiology, Albany Medical College of Union University, New York 12208.
J Appl Physiol (1985). 1987 Aug;63(2):623-33. doi: 10.1152/jappl.1987.63.2.623.
Plasma fibronectin modulates macrophage phagocytic function and can also incorporate into the insoluble tissue pool of fibronectin where it influences endothelial cell adhesion and tissue integrity. We studied the effect of postoperative bacteremia on lung protein clearance in relation to plasma fibronectin levels using the unanesthetized sheep lung lymph fistula model and the effect of infusion of purified human plasma fibronectin on lung protein clearance. Sheep received live Pseudomonas aeruginosa (5 X 10(8) iv) at a time of normal plasma fibronectin (590 +/- 37 micrograms/ml) or 5 days later at a time corresponding to elevation of plasma fibronectin (921 +/- 114 micrograms/ml). After the first bacterial challenge, there was a 22% decrease (P less than 0.05) in plasma fibronectin. Lung lymph flow (QL) initially increased 308% (P less than 0.05) by 2 h (0 h = 4.7 +/- 1.1 ml/h; 2 h = 14.4 +/- 3.5 ml/h), and the total protein lymph-to-plasma concentration ratio (L/P) declined. This was followed by a sustained second phase response over 3-12 h which was characterized by a 202-393% elevation in QL (P less than 0.05), an increase in the L/P ratio, and a 240-480% (P less than 0.05) increase in lung transvascular protein clearance (TVPC = QL X L/P). Sheep with elevated fibronectin levels also manifested the early (2 h) elevation in QL (P less than 0.05) coupled with a decline in L/P ratio after the second bacterial challenge, but the second-phase increase in TVPC was markedly attenuated. Intravenous infusion of 500 mg of human plasma fibronectin into normal sheep to elevate the fibronectin level comparable to that in the hyperfibronectinemic sheep also attenuated (P less than 0.05) the second-phase (3-12 h) increase in lung protein clearance with sepsis. Thus elevation of plasma fibronectin during postoperative Gram-negative bacteremia may protect the lung vascular barrier. This response may be mediated by either fibronectin's opsonic support of phagocytic function or its influence on lung endothelial cell adhesion.
血浆纤连蛋白可调节巨噬细胞的吞噬功能，还能整合到纤连蛋白的不溶性组织池中，在那里它影响内皮细胞黏附和组织完整性。我们使用未麻醉的绵羊肺淋巴瘘模型研究了术后菌血症对与血浆纤连蛋白水平相关的肺蛋白清除的影响，以及输注纯化的人血浆纤连蛋白对肺蛋白清除的影响。绵羊在血浆纤连蛋白水平正常（590±37微克/毫升）时静脉注射活的铜绿假单胞菌（5×10⁸），或在5天后血浆纤连蛋白升高（921±114微克/毫升）时注射。首次细菌攻击后，血浆纤连蛋白下降了22%（P<0.05）。肺淋巴流量（QL）最初在2小时内增加了308%（P<0.05）（0小时=4.7±1.1毫升/小时；2小时=14.4±3.5毫升/小时），总蛋白淋巴与血浆浓度比（L/P）下降。随后在3至12小时内出现持续的第二阶段反应，其特征是QL升高202 - 393%（P<0.05），L/P比值增加，肺跨血管蛋白清除率（TVPC = QL×L/P）增加240 - 480%（P<0.05）。纤连蛋白水平升高的绵羊在第二次细菌攻击后也表现出QL早期（2小时）升高（P<0.05），同时L/P比值下降，但TVPC的第二阶段增加明显减弱。向正常绵羊静脉输注500毫克人血浆纤连蛋白以提高纤连蛋白水平至与高纤连蛋白血症绵羊相当的水平，也减弱了（P<0.05）败血症时肺蛋白清除的第二阶段（3 - 12小时）增加。因此，术后革兰氏阴性菌血症期间血浆纤连蛋白的升高可能保护肺血管屏障。这种反应可能是由纤连蛋白对吞噬功能的调理支持或其对肺内皮细胞黏附的影响介导的。
