Biology Reference
In-Depth Information
central, peripheral, and enteric nervous systems of many species. It belongs to a
family of bioactive peptides, the tachykinins, a group that also includes NK-A and
NK-B. SP acts in the CNS as a neurotransmitter/neuromodulator affecting behavior
and the neurochemical response to stress—both psychological and physical stress. It
coordinates the response to stress by interacting with the HPA axis and the SNS. In
the dorsal horn of the spinal cord, SP is involved in sensory, and most notably noci-
ceptive, pathways. In the periphery, SP has been identified in C-type sensory nerve
endings and autonomic afferents throughout the body
[8]
. Inoculation of the skin
with SP induces vasodilatation and increases vascular permeability, which, with its
chemoattractant properties, facilitates traffic to sites of inflammation and contributes
to urticaria. CGRP is less potent, but it can potentiate the effects of SP and alone
causes marked vasodilation and hyperemia in the skin
[7]
. SP, as well as histamine,
causes the formation of focal reversible endothelial gaps between endothelial cells
of the vasculature, which is responsible for the increase in vascular permeability
[9]
.
SP, as well as other sensory neuropeptides, may also interact with receptors on mast
cells, which degranulate and release several inflammatory mediators, such as hista-
mine; this reaction can itself cause urticaria and may further enhance the neurogenic
inflammatory response
[10]
. Histamine can also bind to a histamine receptor on the
sensory nerve, producing a prodromic nerve impulse up the sensory nerve and an
antidromic impulse down another axon, resulting in a further release of SP and/or
other sensory neuropeptides and further inflammation
[11]
. Thus, neurogenic inflam-
mation may be evident at a site distant from the original exposure.
In addition to its role in neurogenic inflammation, SP is involved in immunologi-
cal inflammation as well. Lymphocytes and macrophages have receptors for SP, and
these cells can be stimulated by SP to produce cytokines
[7,12]
. Hence, macrophages
stimulated by SP produce the inflammatory mediators prostaglandin (PG)-E2,
thromboxane B2, and superoxide ions
[12]
. It is of interest that SP down-regulates
the synthesis of the anti-inflammatory cytokine TGF-
[13]
. These results suggest
a mechanism whereby SP may also act as a pro-inflammatory mediator by limit-
ing the production of TGF-. Moreover, it was shown that treatment with SP alone
did not enhance IL-10 secretion in either freshly isolated or cultured cord blood
monocytes (FICBM), whereas treatment with SP in combination with lipopolysac-
charide (LPS) leads to a synergistic interaction in up-regulation of IL-10 secretion.
Fragments of SP (SP1-4 and SP5-11), whether in the presence or absence of LPS,
show little effects on IL-10 secretion. SP reverses the inhibitory effect of interferon
(IFN)- on LPS-induced IL-10 secretion by FICBM. In addition, SP antagonists and
anti-SP polyclonal antibodies blocked the SP effect on IL-10 secretion, indicating
that these effects are specific and mediated by the SP receptor
[14]
. Because SP is
the classic mediator of neurogenic inflammation, and because SP can also stimulate
immune cells to produce and release classic pro-inflammatory cytokines (TNF-,
IL-1, and IL-6), SP may serve as a key mediator in the transition of neurogenic
to immunological inflammation. Thus, the route of communication between the
immune and nervous systems is receptor and mediator sharing. Neural cells express
cytokine receptors and produce neurohormones, neurotransmitters, and neuropep-
tides, whereas immune cells express receptors for neurohormones, neurotransmitters,
