REDUCED IN-VIVO PLASMA FIBRONECTIN CONTENT OF LUNG MATRIX DURING POSTOPERATIVE SEPSIS

Sepsis after surgery, trauma, or burn contributes to altered lung endo thelial permeability and respiratory failure. Fibronectin (Fn), an ops onic and adhesive glycoprotein, exists in both a soluble form in plasm a and an insoluble form in the extracellular matrix (ECM). Recent stud ies [E. M. Wheatley, P. J. McKeown-Longo, P. A. Vincent, and T. M. Sab a, Am. J. Physiol. 265 (Lung Cell. Mol. Physiol. 9): L148-L157, 1993] suggest that the ECM content of Fn may influence lung vascular permeab ility. We evaluated the incorporation of plasma-derived Fn (pFn) into the ECM of the lung during postoperative sepsis. Postoperative nonsept ic and postoperative septic rats were compared, using a model of lapar otomy followed by cecal ligation and puncture. To label the pFn pool, rats received intravenously 3 mu g of purified rat I-125-labeled Fn/10 0 g body weight 6 h after surgery (laparotomy). I-125-Fn in the deoxyc holate detergent-insoluble fraction of tissues was used to quantify ma trix-incorporated Fn at 4 h after infusion with I-125-Fn. Septic rats exhibited a peripheral leukopenia as well as reduction in plasma volum e, Fn half-life, and total pFn pool. Incorporation of pFn in the liver and spleen of postsurgical septic rats was not different (P > 0.05) f rom sham-operated (postsurgical nonseptic) rats, but incorporation was significantly decreased (P < 0.05) in vivo in the lung. However, unde r controlled in vitro conditions, lung tissue harvested from septic or sham-operated rats demonstrated a similar tissue incorporation of sol uble I-125-pFn as well as similar rates of retention/turnover of ECM I -125-Fn, based on pulse-chase experiments; These data suggest that the in vivo inflammatory environment;in the lung during postoperative sep sis, 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 sep sis.