Cloning and characterization of SDF‐1γ, a novel SDF‐1 chemokine transcript with developmentally regulated expression in the nervous system

Gleichmann, Marc; Gillen, Clemens; Czardybon, Margarete; Bosse, Frank; Greiner–Petter, Regine; Auer, Johannes; Müller, Hans

doi:10.1046/j.1460-9568.2000.00048.x

Cited by 129 publications

(107 citation statements)

References 30 publications

(94 reference statements)

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“…4,80,81,84 SDF-1 is produced by astrocytes, macrophages, neurons and Schwann cells. 83,[86][87][88] An increase in SDF-1 mRNA has been detected in HIV encephalitis 79 and protein expression of SDF-1 also appears to be elevated in the brains of HIV patients. 89 To what degree the increased expression of SDF-1 aggravates neuronal damage by HIV-1 remains to be shown.…”

Section: Chemokine Receptors In Hiv-1 Infection and Hadmentioning

confidence: 98%

“…67,69,101-103 SDF-1 transcripts are predominantly expressed by oligodendrocytes, astrocytes and neurons in the neocortex, hippocampus and cerebellum 87,103 and by meningeal cells. 102 In vitro, the production of SDF-1 by purified astrocyte cultures is associated with a macrophageastrocyte interaction.…”

Section: Effect Of Chemokines and Hiv/gp120 On Neural Stem And Progenmentioning

confidence: 99%

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HIV-1 infection and AIDS: consequences for the central nervous system

et al. 2005

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Infection with the human immunodeficiency virus-1 (HIV-1) can induce severe and debilitating neurological problems that include behavioral abnormalities, motor dysfunction and frank dementia. After infiltrating peripheral immune competent cells, in particular macrophages, HIV-1 provokes a neuropathological response involving all cell types in the brain. HIV-1 also incites activation of chemokine receptors, inflammatory mediators, extracellular matrix-degrading enzymes and glutamate receptor-mediated excitotoxicity, all of which can trigger numerous downstream signaling pathways and disrupt neuronal and glial function. This review will discuss recently uncovered pathologic neuroimmune and degenerative mechanisms contributing to neuronal damage induced by HIV-1 and potential approaches for development of future therapeutic intervention.

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Section: Chemokine Receptors In Hiv-1 Infection and Hadmentioning

confidence: 98%

Section: Effect Of Chemokines and Hiv/gp120 On Neural Stem And Progenmentioning

confidence: 99%

HIV-1 infection and AIDS: consequences for the central nervous system

et al. 2005

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“…The cDNAs corresponding to CXCL12␣ and CXCL12␤ encode proteins of 89 and 93 amino acids, respectively. A third splice variant, classified as CXCL12␥, has been identified in rats (14). The human equivalent of CXCL12␥ was recently identified among other splice variants of CXCL12 (33).…”

mentioning

confidence: 99%

The Potent Anti-HIV Activity of CXCL12γ Correlates with Efficient CXCR4 Binding and Internalization

Altenburg

Alkhatib

et al. 2010

J Virol

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We previously demonstrated that the naturally occurring splice variant stromal cell-derived factor 1␥/ CXCL12␥ is the most potent CXCL12 isoform in blocking X4 HIV-1, with weak chemotactic activity. A conserved BBXB domain (B for basic and X for any residue) located in the N terminus ( 24 KHLK 27 ) is found in all six isoforms of CXCL12. To determine whether the potent antiviral activity of CXCL12␥ is due to the presence of the extra C-terminal BBXB domains, we mutated each domain individually as well as in combination. Although binding of CXCL12␥ to heparan sulfate proteoglycan (HSPG) was 10-fold higher than that observed with CXCL12␣, the results did not demonstrate a direct correlation between HSPG binding and the potent antiviral activity. CXCL12␥ mutants lacking the conserved BBXB domain (designated ␥B1) showed increased binding to HSPG but reduced anti-HIV activity. In contrast, the mutants lacking the C-terminal second and/or third BBXB domain but retaining the conserved domain (designated B2, B3, and B23) showed decreased binding to HSPG but increased anti-HIV activity. The B2, B3, and B23 mutants were associated with enhanced CXCR4 binding, receptor internalization, and restored chemotaxis. Internalization of CXCR4 was more potent with CXCL12␥ than with CXCL12␣ and was significantly reduced when the conserved BBXB domain was mutated. We concluded that the observed potent anti-HIV-1 activity of CXCL12␥ is due to increased affinity for CXCR4 and to efficient receptor internalization.Chemokines are small, structurally related chemoattractant cytokines characterized by conserved cysteine residues. Based on the positions of the first N-terminal cysteines, chemokines fall into four subfamilies. The CC and CXC subfamilies have been well characterized. The CC subfamily includes the following: regulated on activation, normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory peptides 1 (MIP-1). The prototype of the CXC subfamily is interleukin-8 (IL-8)/ CXCL8. The C chemokine (lymphotactine) and CX3C chemokine (fractalkine) subfamilies were recently identified (reviewed in reference 30). The physiological activities of chemokines are mediated by the selective recognition and activation of chemokine receptors belonging to the seven-membrane-domain G-protein-coupled receptor superfamily (GPCRs). In addition, chemokines also bind to glycosaminoglycans (GAGs) through distinct binding sites. Chemokine binding to GAGs on cells, particularly endothelial cells, results in chemotactic chemokine gradients that allow correct presentation of chemokines to leukocytes, therefore enabling target cells to cross the endothelial barrier and migrate into tissues (reviewed in reference 10).Stromal cell-derived factor 1 (SDF-1)/CXCL12 is a member of the CXC chemokine family and is a key regulator of B-cell lymphopoiesis, hematopoietic stem cell mobilization, and leukocyte migration (reviewed in reference 10). CXCL12 was originally thought to mediate these processes through...

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“…The cDNAs corresponding to CXCL12␣ and CXCL12␤ encode proteins of 89 and 93 amino acids, respectively. A third splice variant, classified as CXCL12␥, has been identified in rats (19). The human equivalent of CXCL12␥ has recently been identified among other splice variants of CXCL12 (41).…”

mentioning

confidence: 99%

A Naturally Occurring Splice Variant of CXCL12/Stromal Cell-Derived Factor 1 Is a Potent Human Immunodeficiency Virus Type 1 Inhibitor with Weak Chemotaxis and Cell Survival Activities

Altenburg

Broxmeyer

et al. 2007

J Virol

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CXCL12/stromal cell-derived factor 1 is a member of the CXC family of chemokines that plays an important role in hematopoiesis and signals through CXCR4 and CXCR7. Two splice variants of human CXCL12 (CXCL12␣ and CXCL12␤) induce chemotaxis of CXCR4 ؉ cells and inhibit X4 infection. Recent studies described four other novel splice variants of human CXCL12; however, their antiviral activities were not investigated. We constructed and expressed all of the CXCL12 splice variants in Escherichia coli. Recombinant proteins were purified through a His affinity column, and their biological properties were analyzed. All six CXCL12 variants induced chemotaxis of CXCR4؉ and CXCR7 ؉ cell lines. Enhancement of survival and replating capacity of human hematopoietic progenitor cells were observed with CXCL12␣, CXCL12␤, and CXCL12 but not with the other variants. CXCL12␥ showed the greatest antiviral activity in X4 inhibition assays and the weakest chemotaxis activity through CXCR4. The order of potency in X4 inhibition assays was as follows: CXCL12␥ > CXCL12␤ > CXCL12␣ > CXCL12 > CXCL12 > CXCL12␦. The order of anti-human immunodeficiency virus (HIV) activity was associated with the number of BBXB motifs present in each variant; the most potent inhibitor was CXCL12␥, with five BBXB domains. The results suggest that the different C termini of CXCL12 variants may contain important molecular determinants for the observed differences in antiviral effects and other biological functions. These studies implicate CXCL12␥ as a potent HIV-1 entry inhibitor with significantly reduced chemotaxis activity and small or absent effects on progenitor cell survival or replating capacity, providing important insight into the structure-function relationships of CXCL12.Chemokines are small, structurally related chemoattractant cytokines, characterized by conserved cysteine residues. Based on the positions of the first N-terminal cysteines, chemokines fall into four subfamilies. The CC and CXC subfamilies have been well characterized. The CC subfamily includes RANTES (for "regulated on activation, normal T-cell expressed, and secreted"), MCP-1 (monocyte chemoattractant protein 1), and MIP-1␤ (macrophage inflammatory protein 1␤). The prototype of the CXC subfamily is interleukin-8 (IL-8). The C chemokine (lymphotactine) and the CX3C chemokine (fractalkine) subfamilies have been identified more recently (reviewed in reference 28). Chemokines signal through Gprotein-coupled seven-transmembrane-domain receptors and are primarily involved in immunosurveillance, activation, and recruitment of specific cell populations during disease (reviewed in reference 28).Stromal cell-derived factor 1 (SDF-1)/CXCL12 is a member of the CXC chemokine family and is a key regulator of B-cell lymphopoiesis, hematopoietic stem cell mobilization, and leukocyte migration (reviewed in reference 28). CXCL12 has also been shown to block human immunodeficiency virus type 1 (HIV-1) infection (reviewed in reference 38). CXCL12 was originally thought to mediate these processes throug...

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Cloning and characterization of SDF‐1γ, a novel SDF‐1 chemokine transcript with developmentally regulated expression in the nervous system

Cited by 129 publications

References 30 publications

HIV-1 infection and AIDS: consequences for the central nervous system

HIV-1 infection and AIDS: consequences for the central nervous system

The Potent Anti-HIV Activity of CXCL12γ Correlates with Efficient CXCR4 Binding and Internalization

A Naturally Occurring Splice Variant of CXCL12/Stromal Cell-Derived Factor 1 Is a Potent Human Immunodeficiency Virus Type 1 Inhibitor with Weak Chemotaxis and Cell Survival Activities

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