Endotoxin-sensitive Factor

S. Limulus Factor C endotoxin-sensitive serine protease zymogen with a mosaic structure of complement-like, epidermal growth factor-like and lectin-like domains. J Biol Chem 266... 

Early research showed that Pb exposure could increase sensitivity to bacterially-derived endotoxins [63] as well as increase production of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-a) by macrophages [64-67], Studies in several species indicate that Pb boosts production of TNF-a both immediately following adult exposure and in later life following gestational exposure. Flohe and coworkers [67] reported that Pb-induced elevation in TNF-a production is sensitive to both protein kinase C signaling as well as protein production. Not only can the production of TNF-a be elevated following exposure to Pb, but also the expression of the receptor for TNF-a (TNF-R) is elevated [68], Therefore, the combined effect of elevated cytokine production by macrophages as well as increased receptor expression would be expected to contribute to problematic inflammatory responses. 

Dentener, M.A.et al., Role of tumor necrosis factor in the enhanced sensitivity of mice to endotoxin after exposure to lead, Immunopharmacol. Immunotoxicol. 11, 321, 1989. 

Endotoxin unit/ml = dilution factor of last end point (D.F.) x LAL reagent sensitivity... 

Fig. 9.5 Molecular cloning and expression of Factor C in the baculo viral system and expression in insect cells produced an rFC with remarkable sensitivity of 0.001 EU/mL endotoxin. (B BamHl, E EcoRI, X Xhol, H Hindlll, P PstI, N Ncol)...

The results of endotoxin tests for in-process solutions, bulk materials, and finished parenteral products should be reported in the same units as those assigned to the product. Two factors determine the sensitivity of a BET. For infusion solutions and device extracts, the gel-clot sensitivity or the lowest point on the standard curve (lambda for kinetic LAL) and the amount of dilution determine test sensitivity.For products that have an endotoxin limit in EU/mg, the choice of lambda and the concentration of the test material determine sensitivity. The formula for product-specific sensitivity (PSS) is a convenient way to calculate the sensitivity of a BET for this type of product, where ... 

Ishii, S., Kuwaki, T., Nagase, T., Maki, K., Tashiro, F., Sunaga, S., Cao, W. H., Kume, K., Fukuchi, Y., Ikuta, K., Miyazaki, J. I., Kumada, M., and Shimizu, T. (1988). Imparied anaphylactic responses with intact sensitivity to endotoxin in mice lacking a platelet-activating factor receptor. J. Exp. Med. 187, 1779-1788. 

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