Mechanism of acute depletion of plasma fibronectin following thermal injury in rats. Appearance of a gelatinlike ligand in plasma.

Plasma fibronectin was depleted within 15 min following sublethal burn, followed by partial recovery at 8 h and complete restoration by 24 h in anesthetized rats. Radiolabeled 75Se-plasma fibronectin, injected intravenously before burn, was rapidly sequestered in burn skin as well as the liver. Fibronectin levels at 2 h postburn as detected by immunoassay vs. 75Se-plasma fibronectin indicated that more fibronectin was in the plasma than detected by electroimmunoassay. Crossed immunoelectrophoretic analysis of fibronectin in early postburn plasma demonstrated a reduced electrophoretic mobility of the fibronectin antigen. Addition of heparin or fibrin, both of which have affinity for fibronectin, to normal plasma was unable to reproduce this altered fibronectin electrophoretic pattern. In contrast, addition of gelatin or native collagen to normal plasma reproduced the abnormal electrophoretic pattern of fibronectin seen in burn plasma. Extracts of burned skin, but not extracts of normal skin, when added to normal plasma, elicited a similar altered electrophoretic pattern for fibronectin. By gel filtration, fibronectin in burn plasma had an apparent molecular weight approximately 40% greater than that observed in normal plasma. These data suggest the release into the blood of a gelatinlike ligand from burned skin, which complexes with plasma fibronectin. Thus, fibronectin deficiency acutely postburn appears mediated by (a) its accumulation at the site of burn injury; (b) its removal from the circulation by the liver; and (c) its presence in the plasma in a form that is less detectable by immunoassay.

Normal fibronectin levels as a function of age in the pediatric population.

Fibronectin is an important non-immune opsonic protein influencing phagocytic clearance of blood-borne nonbacterial particulates which may arise in association with septic shock, tissue injury, and intravascular coagulation. In the present study, serum fibronectin was measured by both electroimmunoassay as well as rapid immunoturbidimetric assay in healthy children (n = 114) ranging in age from 1 month to 15 years in order to delineate the temporal alterations in fibronectin with age. Normal adult serum fibronectin concentrations are typically 220 micrograms/ml +/- 20 micrograms/ml. Serum concentration is 35-40% lower than normal plasma concentration due to the binding of fibronectin to fibrin during clot formation. Children between 1-12 months of age had significantly (P less than 0.05) lower serum fibronectin levels than children between the ages of 1-15 years. Progressive elevation in fibronectin levels was observed within the last 8 months of the first year of age. Fibronectin levels in children older than 1 year of age remained constant up to 15 years and were within the lower limit of the normal adult concentration. No significant (P greater than 0.05) difference in serum fibronectin was observed between male and female children at all age groups. Fibronectin levels thus, increase during the first year of age and normal levels of this blood protein in the infant are less than the normal range for adults.

Influence of septic peritonitis on circulating fibronectin, immunoglobulin, and complement: relationship to reticuloendothelial phagocytic function.

This study was designed to quantify the changes in the major serum opsonins--ie, fibronectin, IgG, and C3--during Staphylococcus aureus and Escherichia coli peritonitis as they may functionally relate to RES phagocytic function. Both forms of peritonitis were characterized by acute depletion of fibronectin, IgG, and C3 within 6 h. By 24 h, C3 levels had returned to control levels in both groups. IgG levels remained depressed 24 h following the induction of E coli peritonitis but had normalized by 24 h after Staph aureus challenge. In contrast, fibronectin was markedly elevated by 24 h with both E coli and Staph aureus peritonitis. Hepatic RES phagocytic function was significantly stimulated following induction of either Staph aureus or E coli peritonitis. The rapid increase in fibronectin as well as RES activation during septic peritonitis may represent a generalized host-defense response.

Comparative influence of blood-borne nonbacterial particles and Staphylococcus aureus on fibronectin, complement and immunoglobulin.

Opsonic fibronectin deficiency has been documented in septic injured patients and suspected to reflect acute depletion due to blood-borne nonbacterial particulates. In the present study, the comparative effect of intravenous infusion of heat-killed Staphylococcus aureus or gelatin-coated nonbacterial test particles on immunoreactive fibronectin, IgG and C3 was investigated. These two test particles were selected because of their known dependence upon adequate opsonization for efficient RES phagocytic removal. The intravenous injection of gelatin-coated RE test lipid emulsion (50 mg/100 gm body weight) resulted in an acute depletion of serum fibronectin with no major alteration in circulating IgG or C3. This selective depletion of fibronectin was followed by a rapid restoration and elevation of fibronectin level within 24 hours. In contrast, intravenous infusion of heat-killed S. aureus (1 X 10 11/rat) resulted in an acute depletion of fibronectin and C2 within 60 minutes. The deficiency of these opsonic proteins after bacterial challenge was followed by elevation of fibronectin and normalization of C2. IgG was not significantly changed at any time. The decline in fibronectin and C3 was greater with an increase in bacterial dose. These studies emphasize the specificity of the opsonic deficiency induced by gelatin-coated particles. Additionally, the suggest that opsonic deficiency with S. aureus bacteremia may be, in part, functionally related to disturbances of fibronectin. The role of fibronectin deficiency in documented states of opsonic deficiency with sepsis warrants consideration.