It is commonly acknowledged that the nervous system and the immune
system, those most complex of networks, share attributes beyond
their intricacy. Elements common to the two systems include memory,
connectivity, flexibility and developmental selection of cellular
composition by a rigorous process involving widespread programmed
cell death. There is one salient difference: the cells of the
immune system are predominantly in constant motion, while
post-mitotic neurons and glia are largely fixed in place.
Therefore, chemokines, initially characterized as leukocyte
chemoattractants, have for the last one and one-half decades been
intensely and productively studied in the contexts of inflammation,
immunity and hematopoietic development. Only recently have the two
fields, neurobiology and immunology, displayed mutual interests in
chemokines. This convergence of the two tribes of investigators was
catalyzed by the finding that SDF-1 (now known as CXCL12) and its
receptor, CXCR4, exerted significant and similar functions in
development of both nervous and immune systems. Indeed CXCL12 and
CXCR4 were required, in an uncannily similar fashion, for retention
of pre-B lymphocytes at sites of maturation in the bone marrow and
of neuronal progenitors in the external granule cell layer of the
developing cerebellum. Recent reports indicate that chemoattraction
of cerebellar granule cells through CXCR4 can be suppressed by
reverse signaling initiated by binding of soluble eph receptors to
transmembrane ephrin B, thereby establishing a link between
chemokine action and a cardinal patterning system of the developing
nervous system. As may be anticipated when a dam breaks, a massive
influx of correlative observations in the nervous and immune
systems is likely to ensue.
This volume represents the state of current knowledge. To this end,
introductory material for both systems is provided. Basic and
advanced 'chemokinology' are presented. The recipe for making a
nervous system (both ingredients and instructions for preparation)
is described, as are the roles of chemokines and their receptors in
making an immune system. Given their importance and complexity,
CXCL12/CXCR4 interactions are separately treated in varying
contexts.
The field of 'neurobiology of chemokines' has not lain fallow
during the last ten years. During much of this time the principal
focus has been on neuroinflammation. Linking the immune and nervous
systems are explanations of the functions of chemokines and their
receptors for resident brain macrophages, the microglia, the unique
cerebrovascular endothelium and angiogenesis.
Understanding human disease is the goal of much of this research.
New discoveries are being made and reported at a gratifying rate.
It is expected that this volume will promote the steady production
and application of useful new knowledge in this developing field.
It provides a unique single-source database for basic neurobiology
highlighting the fundamental aspects of chemokines and discussing
the relations of chemokine science to animal models and human
disease.
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