DELAYED ELEVATION OF ED(1)-CELLULAR FIBRONECTIN IN PLASMA FOLLOWING POSTSURGICAL BACTEREMIA

Fibronectin (Fn) exists in both a soluble form in plasma and lymph as well as an insoluble form in the extracellular matrix. Matrix-localize d cellular fibronectin (cFn) contains extra domains (ED(1) and/or ED(2 )) not found in plasma Fn (pFn). Very little ( < 1-2%) ED(1)-containin g cFn exists in normal blood, and its rapid release into plasma and/or lymph is believed to reflect acute vascular injury. We used a poly- c lonal antibody to sheep pFn and a monoclonal antibody to ED(1) domain of cFn to measure both pFn and ED(1)-cFn in relationship to lung lymph flow (Q(L)), lung lymph-to-plasma (L/P) total protein concentration r atio, and lung protein clearance (LPC). Unanesthetized sheep (n = 7) w ere injected intravenously with Pseudomonas aeruginosa (5 x 10(8)) at both 2 and 7 days following surgical preparation of a lung lymph fistu la. After both bacterial challenges, we observed an early increase in Q(L) and a small decline in the L/P ratio (0-2 h), reflecting increase d fluid filtration in the presence of an intact vascular barrier. This was followed by a further increase (P < 0.05) in Q(L); an elevation i n the L/P ratio; and a marked (P < 0.05) increase in LPC over 3-6 h, i ndicative of an increase in lung endothelial protein permeability. Bef ore the first bacterial infusion, ED(1)-cFn in plasma was 9.97 mu g/ml or similar to 2% of the total Fn antigen in plasma; whereas ED(1)-cFn in lung lymph was 6-8% of total lymph Fn. However, by 5 days after th e first bacterial infusion, baseline ED(1)-cFn in plasma increased (P < 0.05) sixfold. ED(1)-cFn flux (lymph ED(1)-cFn x Q(L)) into lung lym ph increased early after both challenges. This was followed by a decli ne of ED(1)-cFn flux over 3-6 h after the 1st challenge, whereas after the second bacterial challenge, the high blood levels of ED(1)-cFn re sulted in a sustained elevation in ED(1)-cFn flux into lymph in associ ation with altered lung vascular permeability. Thus, after postsurgica l bacteremia, the early release of ED(1)-cFn into lung lymph prior to the increase in lung vascular permeability is followed by a delayed el evation of ED(1)-cFn in the blood within 3-5 days. This may reflect it s release from cells involved in a reparative process to restore lung vascular integrity.