Macrophages expressing a fusion protein derived from bactericidal/permeability-increasing protein and IgG are resistant to endotoxin

Peter S. Dahlberg, Robert D Acton, Marc E. Uknis, Hanz G. Klaerner, Jennifer W. Johnston, Christopher D. Levelle, Beulah H. Gray, David L. Dunn

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1173-1178
Number of pages6
JournalArchives of Surgery
Volume131
Issue number11
DOIs
StatePublished - Nov 1996

Fingerprint Dive into the research topics of 'Macrophages expressing a fusion protein derived from bactericidal/permeability-increasing protein and IgG are resistant to endotoxin'. Together they form a unique fingerprint.

Cite this