Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation.
Chemokines are small secreted proteins that stimulate the directional migration of leukocytes and mediate inflammation. 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 delta-chemokine family and that it may play a role in brain inflammation processes.
Pan
Y
Y
Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA. pan@mpi.com
Lloyd
C
C
Zhou
H
H
Dolich
S
S
Deeds
J
J
Gonzalo
J A
JA
Vath
J
J
Gosselin
M
M
Ma
J
J
Dussault
B
B
Woolf
E
E
Alperin
G
G
Culpepper
J
J
Gutierrez-Ramos
J C
JC
Gearing
D
D
D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002633:Chemotaxis; D002885:Chromosomes, Human, Pair 16; D003545:Cysteine / Q000032:analysis; D029721:Drosophila Proteins; D004660:Encephalitis / Q000378:metabolism*; D004926:Escherichia coli; D006801:Humans; D007124:Immunoenzyme Techniques; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins; D017386:Sequence Homology, Amino Acid; D015854:Up-Regulation
D018925:Chemokines; D029721:Drosophila Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C066176:Nrt protein, Drosophila; D011994:Recombinant Proteins; D003545:Cysteine