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 journalArticlepeer-review

5 Scopus citations


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
Issue number11
StatePublished - Nov 1996

Bibliographical note

Funding Information:
Supported by grant R01-GM32414from the National In¬ ofHealth, Bethesda, (Dr Dunn). Presentedatthe16thAnnualMeetingoftheSurgi¬ cal Infection Society, Milwaukee, Wis, April 25, 1996. Correspondingauthor:DavidL.Dunn,MD,PhD,Box ware242UniversitySt ofMN55455.MinnesotaHealthCenter,420Dela¬ SE, Minneapolis,

Copyright 2018 Elsevier B.V., All rights reserved.

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