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cytological studies revealed that meprins are involved in the hematological system.
Interestingly, meprin dKO mice exhibit a disturbance of monocytes and natural
killer cells (Sun et al. 2009 ). Flow cytometrical analysis showed that deficiency in
both meprins results in an underpresentation of the CD11b
resi-
dent monocytes (R-MC) in the peripheral blood (Fig. 4.8 ). In correlation with this
abnormality is an increase in the prevalence of CD11b
þ
/CD14
þ
/Ly6c
inflam-
matory monocytes (I-MC) in the bone marrow. R-MC are mature monocytes which
are mostly developed from the I-MC (Auffray et al. 2009 ). Interestingly, NK cells
in the dKO mice are also decreased in blood and increased in the bone marrow, but
T and B lymphocytes are not significantly affected by meprin deficiency.
The exact mechanisms underlying the disturbed distribution of these select
leukocytes remain undetermined. The accumulation of meprin deficient leukocytes
in the bone marrow was not due to a block of the leukocyte development in bone
marrow. Along the process of NK cell development, progenitors of the NK lineage
sequentially acquire the expression of CD122, NK1.1, and CD49b, which provides
þ
/CD14
þ
/Ly6c
þ
Blood
Bone Marrow
a
b
c
CD14 + /Ly6c ++
CD14 + /Ly6c -
CD14 + /Ly6c ++
10 4
10 4
10 4
10 3
10 3
10 3
10 2
10 2
10 2
10 1
10 1
10 1
10 0
10 0
10 0
10 0
10 1
CD14 FITC
10 2
10 3
10 4
10 0
10 1
CD14 FITC
10 2
10 3
10 4
10 0
10 1
CD14 FITC
10 2
10 3
10 4
d
30%
25%
dKO
p
<0.05*
dWT
22.4%
17.9%
20%
15%
10%
5%
0%
p = 0.84
p
<0.01*
6.2%
2.7%
2.3%
2.4%
CD14+/Ly6c ++
CD14+/Ly6c -
Blood
CD14+/Ly6c ++
Bone Marrow
Fig. 4.8 Monocyte changes in blood and bone marrow of dKO mice compared to WT mice. In
comparison to WT mice, double knockout (dKO) mice had low CD14 þ /Ly6c resident monocytes
in blood, but high CD14 þ /Ly6c þþ inflammatory monocytes in bone marrow. Peripheral blood and
bone marrow cells were stained with CD14-fluorescein isothiocyanate, Ly6c-phycoerythrin, and
CD45-peridinin chlorophyll, followed by flow cytometry. Representative dot plots (a-c) are to
show cell populations compared in (d). Darker events are the gated cells in CD14/Ly6c plots.
Granulocytes were excluded by gating in the FSC/SSC plots (not shown). Data were from two
independent experiments with a total of seven mice in each group (Sun et al. 2009 )
 
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