The Relationship between CIG Depletion and Peripheral Neutrophil Function in Rabbits and Man

Abstract

Patients, after major thermal injury, develop predictable abnormalities in neutrophil function, especially during septic episodes. These abnormalities include a decrease in chemotactic ability and impaired intracellular killing of bacteria. Bacterial phagocytosis usually remains normal. Recent evidence has accumulated indicating that levels of cold-insoluble globulin (plasma fibronectin) also decrease during sepsis in patients with thermal injury. The relationship between cold-insoluble globulin (CIG) and peripheral neutrophil function has not been clearly determined, although its importance in optimal reticuloendothelial system function has been established in both human and animal studies. The purpose of the present study was to determine the relationship between circulating cold-insoluble globulin levels and neutrophil function. The rationale for the study was the observation that CIG is present on the surface of many cells, including neutrophils, and that this protein is crucial for coordinated cell-cell and cell-surface interactions of several cell types, including fibroblasts. Therefore it seemed reasonable to determine if depletion of this protein would result in impaired neutrophil chemotaxis or bactericidal activity. To test this hypothesis, nine septic burn patients were studied during 13 septic episodes. Although both neutrophil function and CIG levels decreased in many patients, no consistent correlation between these two parameters was found. Because of the variables inherent in clinical studies an animal model was used to study the effect of isolated CIG depletion on several neutrophil parameters. The results of the animal studies indicated that after CIG depletion, chemotaxis and intracellular killing of bacteria were normal, although phagocytosis of S. aureus was impaired. The neutrophil response that occurred after CIG depletion in the rabbit was not consistent with the documented acquired neutrophil defects present in humans after thermal injury. Therefore although adequate circulating levels of CIG may be important to host resistance after thermal injury, its depression does not appear to have a direct effect on the evolution of the neutrophil dysfunction seen after thermal injury.