Biology Reference
In-Depth Information
TLR4. At this time, it is not known whether moesin acts as an
independent LPS receptor or in unison with CD14/TLR4, although the
latter appears more likely.
outside of cell
inside of cell
LBP
several
kinases
LPS
mCD14
MyD88-
dependent
LBP
moesin
low conc
of LPS
LBP
TLR4
i
κ
B
MyD88
MD-2
LPS
sCD14
JNK
bacterial
lysis
LPS
lipA
low conc
of LPS
MyD88-
independent
IRF3
LPS
CD11/CD18
NF-
κ
B
INF-
β
AP-1
high conc
of LPS
L-selectin
LPS
intracellular
signal
?
Nucleus
cytokine secretion:
TNF-
α
, IL-1
β
, IL-6, etc.
ribosome
Fig. 6.4 Lipid A recognition leading to cytokine secretion.
Another receptor pathway that has been implicated in the recognition
of LPS utilizes CD18 antigens, which are also called CD11/CD18 or β
2
-
integrins. This group of cell membrane glycoproteins was actually
discovered before the CD14 receptor molecule, but due to their lower
affinity for LPS, they have been posited to play only a minor role in its
recognition (Wright and Jong, 1986). LPS stimulation of mononuclear
cells lacking the CD18 receptor indicated that there was another
activation pathway, which later led to the discovery of CD14 (Wright
et al.
, 1990b, 1989). The three known CD18 members, which are all
expressed on leukocytes, are CD11a/CD18 (also known as α
1
β
2
-integrin
and LFA-1), CD11b/CD18 (or α
2
β
2
-integrin, CR3, and MAC-1), and
CD11c/CD18 (or α
3
β
3
-integrin, CR4, p150,95). There is some evidence
that CD11/CD18, much like CD14, signals through TLR4 and is
necessary for optimal production of COX-2, IL-2, and IL-12, but it is not
needed for the LPS-induced expression of cytokines such as
TNFα (Perera
et al.
, 2001, Ingalls and Golenbock, 1995). Other
unidentified molecules may be involved in the recognition of LPS.
