Biology Reference
In-Depth Information
Table 5.2 The timing of expression of the three PLA
2
s, after SCI, the cell types they are
expressed in and their roles
sPLA
2
GIIA
cPLA
2
GIVA
iPLA
2
GVIA
Time
period
expressed
in SCI
Increased 3-7 days
Increased
3-28 days
Increased 7-28 days
Cell types
expressing
PLA
2
s
Astrocytes and
oligodendrocytes; also in
some neurons and
microglia/macrophages
Neurons,
oligodendrocytes
Oligodendrocytes; also
some astrocytes, neurons,
and microglia/
macrophages
Effects in
SCI
Detrimental
Beneficial
Detrimental
CNS autoimmune disease (
Kalyvas et al., 2009
). Unlike in SCI, blocking
cPLA
2
GIVA with AX059 reduced the severity of clinical paralysis during
the initial phase of EAE when treatment was started before the onset of
symptoms. In contrast, blocking iPLA
2
GVIA with FKGK11 gave the most
profound improvement in EAE. This is in striking contrast to the minimal
effects of blocking iPLA
2
in SCI. Further, treatment with the weak pan-
PLA
2
inhibitor (AX115) had no effect in EAE when treatment was given
prior to onset of symptoms, but eliminated the remission phase (i.e., making
EAE worse) when given after the onset of symptoms. Blocking iPLA
2
GVIA
was most effective in EAE while the weak pan-inhibitor (AX115) and the
sPLA
2
GIIA inhibitor (GK115) were most effective in SCI. These two stud-
ies show that members of the PLA
2
superfamily can have very different roles
in different neurological conditions and point to the need to determine their
roles using selective small molecule inhibitors or gene knockout mice.
5. CONCLUSIONS
The inflammation that occurs in the injured spinal cord contributes to
secondary tissue damage and functional loss. It involves all cell types in the
CNS, as well as immune cells from the periphery. Although this innate
immune response mainly involves microglia, peripheral macrophages, and
neutrophils, other cell types such as astrocytes may also contribute by pro-
ducing factors that regulate leukocyte responses. The immune response after
SCI is complex and involves many cell types and molecular pathways. We
have used different approaches to identify several molecular targets that
