mCD14 is expressed primarily on myeloid cells, such as
monocytes, macrophages and
neutrophils (1-3), the cells most sensitive to LPS, and to a
lesser extent on other cells, such as B
cells (8) and a circulating dendritic cell progenitor (9).
CD14 appears to mediate LPS stimulation
of cells that do not express mCD14 (10, 11), such as
endothelial, epithelial and smooth-muscle
cells. CD14 is found in both serum and urine (5).
The binding of LPS to CD14 requires an acute phase protein,
LPS-binding protein (LBP) (16).
The relationship of mCD14, CD14, LPS and LBP is complicated.
At low concentrations of LPS,
LBP is essential for the binding of LPS to CD14, but at high
concentrations, LBP may actually
inhibit binding of LPS to CD14. In addition, CD14 may
compete with mCD14 for LPS (17) and
may serve to help clear LPS (18). These four factors thus
appear to participate in a complex
feedback mechanism of immune regulation involving both
up-regulation and down-regulation
of the inflammatory process triggered by LPS. It is loss of
control of this mechanism that
appears to lead to septic shock. LPS-bound CD14 signals
production of inflammatory cytokines
and other inflammatory proteins, but the mechanism of signal
transduction is unclear. Since
a GPI anchor is not transmembrane, there presumably is
another transmembrane protein on
cells through which LPS-bound CD14 transmits a signal (19).
In addition to its well known role in gram-negative
infections, CD14 likely serves other
functions as well. It recognizes soluble peptidylglycan from
gram-positive cell walls (20), and it
has been reported to bind apoptotic cells and induce their
phagocytosis (21).
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