Recombinant soluble CD14 prevents mortality in mice treated with endotoxin (lipopolysaccharide).
Endotoxic shock is a life-threatening condition mediated by cytokines released after exposure to bacterial LPS/endotoxin. Activation of monocytes and neutrophils by the binding of LPS to the membrane receptor, CD14, plays a key role in this response. Furthermore, a soluble form of the CD14 receptor enhances the endothelial cell response to LPS. We show here that despite the agonist effects of soluble CD14 on the endothelial cell response to LPS, recombinant soluble CD14 is able to protect mice from LPS-induced lethality. This protection appears to be associated with the inhibition of TNF-alpha release. These results suggest that the soluble CD14 receptor may represent a new form of therapy for endotoxic shock in humans.
Haziot
A
A
Division of Molecular Medicine, North Shore University Hospital/Cornell University Medical College, Manhasset, NY 11030, USA.
Rong
G W
GW
Lin
X Y
XY
Silver
J
J
Goyert
S M
SM
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015214:Antigens, Differentiation, Myelomonocytic / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000187:drug effects; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D004731:Endotoxins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha