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Endotoxin-neutralizing capacity of soluble CD14.

Abstract
Luminol-enhanced chemiluminescence was used to determine the effect of soluble CD14 (sCD14) on the endotoxin-inducible generation of reactive oxygen species in human monocytes. It was necessary to mediate lipopolysaccharide (LPS) monocyte-activating capability by serum factors (LPS-binding proteins). sCD14 reduced LPS-inducible monocyte activation in a dose-dependent manner, even in the case of CD14- monocytes, obtained from a patient with paroxysmal nocturnal haemoglobinuria. These monocytes could be activated by opsonized LPS via other receptors. Using anti-mouse Ig-coated microbeads, it was demonstrated in FACS analysis that sCD14 mediates the binding of a mouse monoclonal anti-CD14 antibody (RoMo 1) to a complex of LPS/FITC (fluoroisothiocyanate) and a LPS-binding protein. The release of sCD14 from cultured monocytes was measured using LPS, TNF alpha (tumour necrosis factor), IL1, 4 and 6 (interleukin-1, -4 and -6) and IFN gamma (interferon-gamma) as stimulators. Addition of LPS and TNF alpha led to a dose-dependent increase in sCD14-levels in the culture supernatant, whereas IL1, IL6 and IFN gamma had no significant effect. IL4 dose-dependently depressed spontaneous sCD14 release. It is possible that elevated sCD14-serum levels in polytraumatized patients indicate a natural protective mechanism against excessive monocyte mediator production. Therefore, sCD14 may be a new therapeutic concept in endotoxic shock prevention.
AuthorsC Schütt, T Schilling, U Grunwald, W Schönfeld, C Krüger
JournalResearch in immunology (Res Immunol) Vol. 143 Issue 1 Pg. 71-8 (Jan 1992) ISSN: 0923-2494 [Print] France
PMID1373513 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Endotoxins
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Oxygen
Topics
  • Antigens, CD (immunology)
  • Antigens, Differentiation, Myelomonocytic (immunology)
  • Endotoxins (antagonists & inhibitors, immunology)
  • Humans
  • In Vitro Techniques
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides (immunology)
  • Luminescent Measurements
  • Monocytes (immunology, metabolism)
  • Oxygen (metabolism)
  • Shock, Septic (immunology, prevention & control)
  • Solubility

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