Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation

An Erratum to this article was published on 04 September 1997

Abstract

Chemokines are small secreted proteins that stimulate the directional migration of leukocytes and mediate inflammation1,2,3,4. During screening of a murine choroid plexus complementary DNA library, we identified a new chemokine, designated neurotactin. Unlike other chemokines, neurotactin has a unique cysteine pattern, Cys-X-X-X-Cys, and is predicted to be a type 1 membrane protein. Full-length recombinant neurotactin is localized on the surface of transfected 293 cells. Recombinant neurotactin containing the chemokine domain is chemotactic for neutrophils both in vitro and in vivo. Neurotactin messenger RNA is predominantly expressed in normal murine brain and its protein expression in activated brain microglia is upregulated in mice with experimental autoimmune encephalomyelitis, as well as in mice treated with lipopolysaccharide. Distinct from all other chemokine genes, the neurotactin gene is localized to human chromosome 16q. Consequently we propose that neurotactin represents a new δ-chemokine family and that it may play a role in brain inflammation processes.

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Figure 1: Amino-acid sequence alignment of human and murine neurotactin (abbreviated as NTN).
Figure 2: Sequence alignment of human neurotactin with α-chemokines IL-8 and GRO-α; β-chemokines MCP-1 and RANTES and γ-chemokine lymphotactin.
Figure 3: Murine tissue northern blot probed with a full-length murine neurotactin cDNA probe.
Figure 4: Immunofluorescent labelling of transfected 293 cells.
Figure 5: Chemotaxis assay of recombinant murine neurotactin on purified human neutrophils (a), monocytes (b) and lymphocytes (c).
Figure 6: Neutrotactin-induced recruitment of leukocytes to the peritoneum.
Figure 7: Expression of murine neurotactin in normal, LPS-treated and EAE brain.

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Acknowledgements

We thank F. Lee, G. Duyk, B. Tepper, M. P. Das, J. Lafaille, D. Levinson, S. Lin, P.Stroobant, G. Jia, D. Holtzman, S. McCarthy, D. Michnick and S. Busfield for advice and support. We are grateful for the expert technical assistance of the Millennium sequencing and bioinformatics group.

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Correspondence to Yang Pan.

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Pan, Y., Lloyd, C., Zhou, H. et al. Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation. Nature 387, 611–617 (1997). https://doi.org/10.1038/42491

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