title: Neutrophil-related factors as biomarkers in EAE and MS.
abstract: A major function of T helper (Th) 17 cells is to induce the production of factors that activate and mobilize neutrophils. Although Th17 cells have been implicated in the pathogenesis of multiple sclerosis (MS) and the animal model experimental autoimmune encephalomyelitis (EAE), little attention has been focused on the role of granulocytes in those disorders. We show that neutrophils, as well as monocytes, expand in the bone marrow and accumulate in the circulation before the clinical onset of EAE, in response to systemic up-regulation of granulocyte colony-stimulating factor (G-CSF) and the ELR(+) CXC chemokine CXCL1. Neutrophils comprised a relatively high percentage of leukocytes infiltrating the central nervous system (CNS) early in disease development. G-CSF receptor deficiency and CXCL1 blockade suppressed myeloid cell accumulation in the blood and ameliorated the clinical course of mice that were injected with myelin-reactive Th17 cells. In relapsing MS patients, plasma levels of CXCL5, another ELR(+) CXC chemokine, were elevated during acute lesion formation. Systemic expression of CXCL1, CXCL5, and neutrophil elastase correlated with measures of MS lesion burden and clinical disability. Based on these results, we advocate that neutrophil-related molecules be further investigated as novel biomarkers and therapeutic targets in MS.
authors.affiliation: Holtom-Garrett Program in Neuroimmunology, Department of Neurology,Department of Radiology, Department of Biostatistics, and Graduate Program in Immunology, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Rumble
authors.affiliation: Holtom-Garrett Program in Neuroimmunology, Department of Neurology,Department of Radiology, Department of Biostatistics, and Graduate Program in Immunology, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Huber
authors.affiliation: Department of Neuroimmunology, Max Planck Institute for Neurobiology, 82152 Martinsried, Germany.
authors.forename: Gurumoorthy
authors.initials: G
authors.lastname: Krishnamoorthy
authors.affiliation: Holtom-Garrett Program in Neuroimmunology, Department of Neurology,Department of Radiology, Department of Biostatistics, and Graduate Program in Immunology, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Ashok
authors.initials: A
authors.lastname: Srinivasan
authors.affiliation: Holtom-Garrett Program in Neuroimmunology, Department of Neurology,Department of Radiology, Department of Biostatistics, and Graduate Program in Immunology, University of Michigan, Ann Arbor, MI 48109.
authors.forename: David A
authors.initials: DA
authors.lastname: Giles
authors.affiliation: Holtom-Garrett Program in Neuroimmunology, Department of Neurology,Department of Radiology, Department of Biostatistics, and Graduate Program in Immunology, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Holtom-Garrett Program in Neuroimmunology, Department of Neurology,Department of Radiology, Department of Biostatistics, and Graduate Program in Immunology, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Holtom-Garrett Program in Neuroimmunology, Department of Neurology,Department of Radiology, Department of Biostatistics, and Graduate Program in Immunology, University of Michigan, Ann Arbor, MI 48109 Holtom-Garrett Program in Neuroimmunology, Department of Neurology,Department of Radiology, Department of Biostatistics, and Graduate Program in Immunology, University of Michigan, Ann Arbor, MI 48109 Neurology Service, VA Ann Arbor Healthcare System, Ann Arbor, MI 48105 bmsegal@umich.edu.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Segal
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism*; D054360:Chemokine CXCL1 / Q000097:blood / Q000276:immunology / Q000378:metabolism; D054365:Chemokine CXCL5 / Q000097:blood / Q000276:immunology / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood / Q000276:immunology / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D015854:Up-Regulation / Q000276:immunology
chemical_list: D015415:Biomarkers; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D016188:Receptors, Granulocyte Colony-Stimulating Factor; C445081:myelin oligodendrocyte glycoprotein (35-55); D016179:Granulocyte Colony-Stimulating Factor