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CUTTING EDGE |
Division of Molecular Medicine, North Shore University Hospital, NYU School of Medicine, Manhasset, NY 11030
LPS (endotoxin) and
proinflammatory cytokines (IL-6, IL-1, and TNF-
) 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.
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