Opsonic Fibronectin Deficiency and Sepsis

Abstract

Opsonic fibronectin is known to modulate macrophage (RE cell) and neutrophil Phagocytic function. Its depletion has been documented following trauma, burn, and operation in patients with rapid restoration of normal levels unless bacteremia and/or wound sepsis intervenes. Sepsis is associated with a secondary phase of opsonic fibronectin deficiency. We have observed in burn patients that this secondary phase of opsonic fibronectin depletion following trauma and burn is seen two to three days prior to the onset of clinical sepsis, raising the question of whether this deficiency sensitized the host to the subsequent development of sepsis or whether its deplection was merely an unsuspected sensitive indication of preclinical sepsis. To address the possibility that opsonic fibronectin deficiency might lower resistance to sepsis, Sprague-Dawley rats (200 gm) were partially depleted (35%) of their opsonic fibronectin prior to intraperitoneal inoculation with Staphylococcus aureus. Mortality to S. aureus peritonitis was significantly (p < 0.05) increased in animals with fibronectin deficiency. Furthermore, in control animals, nonsurvival was also associated with significantly (p < 0.05) lower initial fibronectin levels than survival. However, peritonitis itself also resulted in an early (within one hour) depletion of opsonic fibronectin followed by a marked "hyperopsonemia" within 12 hours in both groups. Thus, opsonic fibronectin depletion decreases resistance to sepsis, and the development of sepsis itself will initiate opsonic fibronectin deficiency. Host defense against infection may depend on early restoration and maintenance of normal opsonic fibronectin levels following trauma, burn, and operation, as well as the ability of the host to mount an appropriate hyperopsonemic elevation of fibronectin levels in response to infection.

Monocyte Function following Surgery in Man

“…In the present study, total SOA for mono cytes was determined by chemiluminescence -a technique which has been previously uti lized to detect post-operative opsonic defi ciency for neutrophils [20] -but was found to be little altered after surgery. Reduction of fibronectin may, however, occur in patients undergoing more extensive surgery than that which patients in the present study had and may be partly due to the development of post-operative sepsis [2,9].…”

Normal Fibronectin Levels as a Function of Age in the Pediatric Population

“…Fibronectin deficiency induced by injection of specific antiserum to fibronectin or by injection of gelatinized particles also decreases resistance to experimental trauma and Staphylococcus aureus peritonitis (7,13). Conversely, opsonic deficiency is seen after trauma and the degree of fibronectin deficiency appears to be directly (5,12,13,16) correlated with the extent of trauma.…”

<i>Haemophilus parainfluenzae</i>Endocarditis on Tricuspid Valve

“…The distinct hematuria may be attributed to the deposition of CIC in the kidney. Fibronectin as an indicator of the function of the reticuloendothelial system [9,10] proved to be a reliable parameter in the clinical course of our patient, indicating fail ure or efficacy of antibiotic therapy. Most authors describing Haemophilus endocardi tis recommend antibiotic treatment with ampicillin and aminoglycosides [5,11,12], Of 42 reported cases with H. parainfluenzae en docarditis, 28 received ampicillin as part of their therapy; this resulted in 25 cures and only 3 failures [13], Until now a single case of ampicillin-resistant H. parainfluenzae endo carditis has been reported [14], In our patient ampicillin plus aminoglycoside therapy was not effective, and only a partial remission with tetracycline plus aminoglycosides re sulted.…”