Role of the α‐chemokine stromal cell‐derived factor (SDF‐1) in the developing and mature central nervous system

Abstract

KEY WORDSCXCR4; brain development; cell migration ABSTRACT ␣-chemokines, which control the activation and directed migration of leukocytes, participate in the inflammatory processes in host defense response. One of the ␣-chemokines, CXCL12 or stromal cell-derived factor 1 (SDF-1), not only regulates cell growth and migration of hematopoietic stem cells but may also play a central role in brain development as we discuss here. SDF-1 indeed activates the CXCR4 receptor expressed in a variety of neural cells, and this signaling results in diverse biological effects. It enhances migration and proliferation of cerebellar granule cells, chemoattracts microglia, and stimulates cytokine production and glutamate release by astrocytes. Moreover, it elicits postsynaptic currents in Purkinje cells, triggers migration of cortical neuron progenitors, and produces pain by directly exciting nociceptive neurons. By modulating cell signaling and survival during neuroinflammation, SDF-1 may also play a role in the pathogenesis of brain tumors, experimental allergic encephalitis, and the nervous system dysfunction associated with acquired immunodeficiency syndrome.

Human immunodeficiency virus gp120-induced apoptosis of human neuroblastoma cells in the absence of CXCR4 internalization

“…The effect of gp120 on CXCR4 internalization/surface expression, however, is not reported in their study. Moreover, gp120 internalization was not observed in glial cells (Bachis et al, 2003), which also express CXCR4, thus questioning whether this is a CXCR4-dependent event (Lazarini et al, 2003). Thus, the apparent discrepancy with our findings could be due to various scenarios, including differences in the cell types and experimental approaches, the reported binding of gp120 to other molecules expressed on the neuronal surface, such as glycosphingolipids Long et al, 1994), and/or the expression of unknown CD4-like molecules in granule neurons.…”

“…CXCR4 is the specific receptor for the chemokine CXCL12 (previously known as SDF-1), which orchestrates the development of many areas of the brain as well as other tissues (Lazarini et al, 2003;Tran and Miller, 2003;Zou et al, 1998). CXCR4 can also bind the human immunodeficiency virus (HIV) envelope protein gp120 that induces apoptotic cell death in primary neurons and cell lines (Bachis and Mocchetti, 2004;Catani et al, 2000;Hesselgesser et al, 1997;Kaul and Lipton, 1999;Mattson et al, 2005;Meucci and Miller, 1996).…”

The pleiotropic effects of the SDF-1–CXCR4 axis in organogenesis, regeneration and tumorigenesis

“…However, knockouts of CXCR4 or SDF-1 results in a significant defect of colonization of embryonic bone marrow (BM) by hematopoietic stem cells (HSC), and defect in the development of heart, brain and large vessels. [17][18][19] As a result of this, CXCR4 and SDF-1 knockouts are lethal and these embryos die in utero.…”

Stromal Cell–Derived Factor-1 (SDF-1)/CXCL12 Attenuates Diabetes in Mice and Promotes Pancreatic β-Cell Survival by Activation of the Prosurvival Kinase Akt

“…Stromal cell-derived factor (SDF)-1/CXCL12 is a peptide chemokine initially identified in bone marrow-derived stromal cells and now recognized to be expressed in stromal tissues in multiple organs (1)(2)(3). SDF-1 is 1 of over 40 chemokines for which there are 18 known receptors.…”