Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

ENDOTOXIN NEUTRALIZING PROTEIN INHIBITS THE RESPONSE OF HUMAN PERIPHERAL BLOOD MONONUCLEAR CELLS TO LPS AND NON-LPS STIMULI. • 1045

Endotoxin neutralizing protein (ENP) is the recombinant form of an Atlantic horseshoe crab amebocyte protein with anti-lipopolysaccharide (LPS) activity. It is highly effective as a therapeutic agent in animal models of live bacterial septic shock, as well as models of endotoxemia. We have shown that ENP binds myelocytic, fibroblast and epithelial cell lines. Binding of ENP is independent of CD14 (LPS receptor) expression, however, once bound ENP prevents subsequent LPS binding.

We have examined the effect of ENP on normal human peripheral blood mononuclear cells (PBMC) activated with LPS and non-LPS stimuli in vitro. Human PBMC were treated with ENP and E. coli 0111:B4 LPS, Mycobacterial lipoarabinomannan (LAM), heat-killed E. coli, or heat-killed Streptococccus pneumoniae. Cytokine secretion was measured in 4 and 20 hour supernatants by cytokine specific ELISA.

ENP, at 25 ug/ml, totally inhibited IL-1 beta, IL-6 and TNF alpha synthesis from adherent PBMC stimulated with LPS. Further, ENP was an effective inhibitor of cytokine synthesis from whole mononuclear cells, at concentrations as low as 2.5 ug/ml. ENP was also highly effective as an inhibitor of non-LPS mediated response; cytokine secretion from human monocytes stimulated with Mycobacterial LAM was abrogated by ENP treatment. ENP also blocked cytokine secretion from PBMC stimulated with heat-killed E. coli or S. pneumoniae. Thus, ENP is an effective inhibitor of PBMC responses to both Gram negative and Gram positive bacteria.

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kurt-Jones, E., Thompson, C., Novitsky, T. et al. ENDOTOXIN NEUTRALIZING PROTEIN INHIBITS THE RESPONSE OF HUMAN PERIPHERAL BLOOD MONONUCLEAR CELLS TO LPS AND NON-LPS STIMULI. • 1045. Pediatr Res 39, 177 (1996). https://doi.org/10.1203/00006450-199604001-01067

Download citation

Search

Quick links