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KMID : 0578320090270020251
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Molecules and Cells
2009 Volume.27 No. 2 p.251 ~ p.255
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Inhibitory Effect of a Phosphatidyl Etha-nolamine Derivative on LPS-Induced Sepsis
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Lee Chung-Hyun
An Hyun-Jung
Kim Jung-ln
Lee Hay-Young
Paik Sang-Gi
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Abstract
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Sepsis is the leading cause of death in critically ill patients. Today, around 60% of all cases of sepsis are caused by Gram-negative bacteria. The cell wall component lipopolysaccharide (LPS) is the main initiator of the cascade of cellular reactions in Gram-negative infections. The core receptors for LPS are toll-like receptor 4 (TLR4), MD-2 and CD14. Attempts have been made to antagonize the toxic effect of endotoxin using monoclonal antibodies against CD14 and synthetic lipopolysaccharides but there is as yet no effective treatment for septic syndrome. Here, we describe an inhibitory effect of a phosphatidylethanolamine derivative, PE-DTPA (phosphatidylethanolamine diethyle-netriaminepentaacetate) on LPS recognition. PE-DTPA bound strongly to CD14 (Kd, 9.52 ??10-8 M). It dose depen-d-ently inhibited LPS-mediated activation of human mye-loid cells, mouse macrophage cells and human whole blood as measured by the production of tumor necrosis factor-??(TNF-?? and nitric oxide, whereas other phospho-lipids including phosphatidylserine and phosphatidylethanolamine had little effect. PE-DTPA also inhibited transcription dependent on NF-?첕 activation when it was added together with LPS, and it rescued LPS-primed mice from septic death. These results sug-gest that PE-DTPA is a potent antagonist of LPS, and that it acts by competing for binding to CD14.
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KEYWORD
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CD14, lipopolysaccharide, phospholipids, sepsis, TLR4
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