Rebres R A, Cho E, Rotundo R F, Saba T M
Department of Physiology and Cell Biology, Albany Medical College, New York 12208, USA.
Am J Physiol. 1996 Sep;271(3 Pt 1):L409-18. doi: 10.1152/ajplung.1996.271.3.L409.
Sepsis after surgery, trauma, or burn contributes to altered lung endothelial permeability and respiratory failure. Fibronectin (Fn), an opsonic and adhesive glycoprotein, exists in both a soluble form in plasma and an insoluble form in the extracellular matrix (ECM). Recent studies [E. M. Wheatley, P. J. McKeown-Longo, P. A. Vincent, and T. M. Saba, Am. J. Physiol. 265 (Lung Cell. Mol. Physiol. 9): L148-L157, 1993] suggest that the ECM content of Fn may influence lung vascular permeability. We evaluated the incorporation of plasma-derived Fn (pFn) into the ECM of the lung during postoperative sepsis. Postoperative nonseptic and postoperative septic rats were compared, using a model of laparotomy followed by cecal ligation and puncture. To label the pFn pool, rats received intravenously 3 micrograms of purified rat 125I-labeled Fn/100 g body weight 6 h after surgery (laparotomy). 125I-Fn in the deoxycholate detergent-insoluble fraction of tissues was used to quantify matrix-incorporated Fn at 4 h after infusion with 125I-Fn. Septic rats exhibited a peripheral leukopenia as well as reduction in plasma volume, Fn halflife, and total pFn pool. Incorporation of pFn in the liver and spleen of postsurgical septic rats was not different (P > 0.05) from sham-operated (postsurgical nonseptic) rats, but incorporation was significantly decreased (P < 0.05) in vivo in the lung. However, under controlled in vitro conditions, lung tissue harvested from septic or sham-operated rats demonstrated a similar tissue incorporation of soluble 125I-pFn as well as similar rates of retention/turnover of ECM 125I-Fn, based on pulse-chase experiments. These data suggest that the in vivo inflammatory environment in the lung during postoperative sepsis, which cannot be reproduced in vitro, may alter the Fn content of the ECM of the lung. Such reduced levels of pFn in the lung ECM may be a factor influencing lung vascular integrity during postoperative sepsis.
手术、创伤或烧伤后发生的脓毒症会导致肺内皮通透性改变和呼吸衰竭。纤连蛋白(Fn)是一种具有调理作用和黏附性的糖蛋白,以可溶性形式存在于血浆中,以不溶性形式存在于细胞外基质(ECM)中。最近的研究[E.M.惠特利、P.J.麦基翁 - 隆戈、P.A.文森特和T.M.萨巴,《美国生理学杂志》265卷(肺细胞与分子生理学9):L148 - L157,1993年]表明,Fn在ECM中的含量可能会影响肺血管通透性。我们评估了术后脓毒症期间血浆来源的Fn(pFn)掺入肺ECM的情况。采用剖腹术后盲肠结扎和穿刺模型,对术后非脓毒症大鼠和术后脓毒症大鼠进行比较。为了标记pFn库,大鼠在手术后(剖腹术)6小时静脉注射3微克纯化的大鼠125I标记的Fn/100克体重。在注入125I - Fn后4小时,用组织中脱氧胆酸盐去污剂不溶性部分的125I - Fn来量化掺入基质的Fn。脓毒症大鼠表现出外周白细胞减少以及血浆量、Fn半衰期和总pFn库减少。术后脓毒症大鼠肝脏和脾脏中pFn的掺入与假手术(术后非脓毒症)大鼠没有差异(P>0.05),但在肺中体内掺入显著减少(P<0.05)。然而,在体外可控条件下,基于脉冲追踪实验,从脓毒症或假手术大鼠收获的肺组织显示出可溶性125I - pFn的组织掺入情况相似,以及ECM 125I - Fn的保留/周转速率相似。这些数据表明,术后脓毒症期间肺内的体内炎症环境(无法在体外重现)可能会改变肺ECM中Fn的含量。肺ECM中pFn水平的降低可能是影响术后脓毒症期间肺血管完整性的一个因素。