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November 1996

Macrophages Expressing a Fusion Protein Derived From Bactericidal/Permeability-Increasing Protein and IgG Are Resistant to Endotoxin

Author Affiliations

From the Departments of Surgery (Drs Dahlberg, Acton, Uknis, Klaerner, and Dunn and Ms Johnston and Mr Levelle) and Microbiology (Dr Gray), University of Minnesota, Minneapolis.

Arch Surg. 1996;131(11):1173-1178. doi:10.1001/archsurg.1996.01430230055010

Objectives:  To generate a recombinant fusion protein (FP) based on the endotoxin-binding domain of bactericidal/permeability-increasing protein (BPI) and the constant domain of IgG and to test its ability to inhibit lipopolysaccharide (LPS)-induced macrophage tumor necrosis factor α (TNF-α) secretion.

Design:  A murine macrophage cell line, RAW 264.7, was transfected with a BPI-IgG FP before incubation with LPS. The amount of LPS-induced TNF-α protein secreted was measured and compared with that secreted by cells transfected with a control construct.

Setting:  Basic science research laboratory.

Main Outcome Measure:  Secreted TNF-α protein concentration.

Results:  After transfection, RAW 264.7–cell FP expression was detected in cell lysates and supernatants. At each LPS dose tested, cells transfected with the FP gene secreted less TNF-α than did cells transfected with a control construct.

Conclusions:  The FP possesses substantial antiendotoxin activity, as delineated by inhibition of LPS-induced TNF-α secretion by murine macrophages transfected with the fusion gene construct. In the future, such FP may be used as a clinical reagent to reduce the morbidity and mortality associated with serious gram-negative bacterial infections in surgical patients.Arch Surg. 1996;131:1173-1178

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