The induction of acute phase proteins by lipopolysaccharide uses a novel pathway that is CD14-independent.
LPS (endotoxin) and proinflammatory cytokines (IL-6, IL-1, and TNF-alpha) are potent inducers of acute phase proteins (APP). Since LPS induces high levels of these cytokines after its interaction with CD14, a protein expressed on the surface of monocytes and neutrophils, it has been assumed that CD14 mediates the LPS induction of APP expression. To test this hypothesis, CD14-deficient and control mice were injected with low doses of LPS, and the expression of several APP that are normally up-regulated by LPS was measured. CD14-deficient mice showed no alteration in the induction of APP, including serum amyloid A, LPS-binding protein, fibrinogen, or ceruloplasmin; in contrast, C3H/HeJ mice, which carry a mutation in the Lps gene, do not up-regulate the expression of these proteins. These studies show that the up-regulation of APP by LPS utilizes a non-CD14 receptor and requires a functional Lps gene.
Haziot
A
A
Division of Molecular Medicine, North Shore University Hospital, NYU School of Medicine, Manhasset 11030, USA.
Lin
X Y
XY
Zhang
F
F
Goyert
S M
SM
D000209:Acute-Phase Proteins / Q000096:biosynthesis*; D000818:Animals; D005260:Female; D018950:Lipopolysaccharide Receptors / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL
D000209:Acute-Phase Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides