Biology Reference
In-Depth Information
5.7 Macrophages
Monocytes/macrophages
are innate immune cells whose primary role in immune
protection is phagocytosis of antigens and presentation to other immune cells such as
the CD4 T cell, as well as the production of cytokines. Cytokine gene expression
in a macrophage appears to be a primary target for NE. Interleukin-10 (IL-10) pro-
duction was enhanced by the addition of a AR agonist to lipopolysaccharide (LPS)-
activated human monocytes or mouse peritoneal macrophages
[77-79]
, while IL-12
and TNF- production by monocytes was inhibited
[80-83]
. There is also evidence
that macrophages respond to AR agonists. For example, macrophages responded to
an
2
AR agonist with increased secretion of TNF-
[84]
. In addition, when a human
monocytic cell line was exposed to an
1
AR agonist, the cell produced IL-6
[85]
.
However,
in vitro
stimulation of resting monocytes with LPS induced expression
of the
1
AR, and subsequent agonist exposure caused an increase in the phospho-
rylation of extracellular signal-related kinase (ERK)
[85]
. Cells from children with
juvenile idiopathic arthritis expressed mRNA for the
1
AR and responded to ago-
nist exposure with an increase in IL-6 and TNF- secretion
[86]
. NE also modu-
lated the expression of matrix metalloproteases: expression was inhibited by addition
of a
1
AR, but not a
2
AR, antagonist, suggesting that NE may play a role in joint
destruction in arthritic patients or macrophage-assisted tumor cell invasion into sur-
rounding normal tissue
[87]
. These data suggest that monocytes/macrophages express
multiple adrenergic receptor subsets, and that the inflammatory cytokine response is
inhibited by
2
AR simulation, but enhanced by
1
AR stimulation, whereas the anti-
inflammatory cytokine response by a macrophage appears to be enhanced by NE.
5.8 Dendritic Cells
Dendritic cells
, another antigen-presenting cell (APC) of the innate immune sys-
tem, presents antigen to T cells and mediate their activation. The administration of a
2
AR antagonist
in vivo
enhanced the contact hypersensitivity response, suggesting
that NE stimulation of the
2
AR exerts an inhibitory effect on the cells that partici-
pate in the hypersensitivity response, including dendritic cells
[88]
. This conclusion
was supported by a finding that NE inhibited Langerhans cell migration from the
site of antigen deposition to the site of antigen presentation in the draining lymph
nodes, and that this was an
1
-/
2
AR-dependent effect
[41,89]
. This study proposed
that NE might act as either a chemotactic factor to direct dendritic cell (DC) migra-
tion or a stimulant to affect DC motility. The latter possibility was supported by an
acute restraint stress paradigm in mice that showed an increase in DC migration to
the skin that was prevented by NE depletion
[41]
. In addition, exposure of bone-
marrow-derived DC to NE or a
2
AR agonist reduced either LPS- or protein anti-
gen (KLH)-induced IL-12 release
[80,81,90]
, but facilitated IL-10 release
[90]
. Thus,
NE appears to suppress DC migration as well as inhibiting inflammatory cytokine
release and enhancing anti-inflammatory cytokine release, both of which effects are-
seen in the macrophage, as described in Section 5.7.
