title: Pentraxin-3 is upregulated in the central nervous system during MS and EAE, but does not modulate experimental neurological disease.
abstract: Pentraxin-3 (PTX3), an acute-phase protein released during inflammation, aids phagocytic clearance of pathogens and apoptotic cells, and plays diverse immunoregulatory roles in tissue injury. In neuroinflammatory diseases, like MS, resident microglia could become activated by endogenous agonists for Toll like receptors (TLRs). Previously we showed a strong TLR2-mediated induction of PTX3 in cultured human microglia and macrophages by HspB5, which accumulates in glia during MS. Given the anti-inflammatory effects of HspB5, we examined the contribution of PTX3 to these effects in MS and its animal model EAE. Our data indicate that TLR engagement effectively induces PTX3 expression in human microglia, and that such expression is readily detectable in MS lesions. Enhanced PTX3 expression is prominently expressed in microglia in preactive MS lesions, and in microglia/macrophages engaged in myelin phagocytosis in actively demyelinating lesions. Yet, we did not detect PTX3 in cerebrospinal fluid of MS patients. PTX3 expression is also elevated in spinal cords during chronic relapsing EAE in Biozzi ABH mice, but the EAE severity and time course in PTX3-deficient mice did not differ from WT mice. Moreover, systemic PTX3 administration did not alter the disease onset or severity. Our findings reveal local functions of PTX3 during neuroinflammation in facilitating myelin phagocytosis, but do not point to a role for PTX3 in controlling the development of autoimmune neuroinflammation.
authors.affiliation: Department of Pathology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Ummenthum
authors.affiliation: Department of Pathology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Laura A N
authors.initials: LA
authors.lastname: Peferoen
authors.affiliation: Clinical Neuroimmunology Unit, Dept. of Neuroscience, San Raffaele Hospital, Milan, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Finardi
authors.affiliation: Queen Mary University of London, Blizard Institute, Barts and The London School of Medicine and Dentistry.
authors.forename: David
authors.initials: D
authors.lastname: Baker
authors.affiliation: Queen Mary University of London, Blizard Institute, Barts and The London School of Medicine and Dentistry.
authors.forename: Gareth
authors.initials: G
authors.lastname: Pryce
authors.affiliation: IRCCS Humanitas Clinical and Research Center and Humanitas University, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.affiliation: Deltacrystallon BV, Leiden, The Netherlands.
authors.forename: Malika
authors.initials: M
authors.lastname: Bsibsi
authors.affiliation: IRCCS Humanitas Clinical and Research Center and Humanitas University, Milan, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bottazzi
authors.affiliation: Department of Pathology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Regina
authors.initials: R
authors.lastname: Peferoen-Baert
authors.affiliation: Department of Pathology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: van der Valk
authors.affiliation: IRCCS Humanitas Clinical and Research Center and Humanitas University, Milan, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garlanda
authors.affiliation: Department of Anatomy II, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Kipp
authors.affiliation: Clinical Neuroimmunology Unit, Dept. of Neuroscience, San Raffaele Hospital, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Furlan
authors.affiliation: Deltacrystallon BV, Leiden, The Netherlands.
authors.forename: Johannes M
authors.initials: JM
authors.lastname: van Noort
authors.affiliation: Department of Pathology, VU University Medical Centre, Amsterdam, The Netherlands.|Queen Mary University of London, Blizard Institute, Barts and The London School of Medicine and Dentistry.
authors.forename: Sandra
authors.initials: S
authors.lastname: Amor
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology* / Q000473:pathology; D002097:C-Reactive Protein / Q000008:administration & dosage* / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D038602:Mice, Biozzi; D017628:Microglia / Q000276:immunology; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology; D009186:Myelin Sheath / Q000378:metabolism; D010587:Phagocytosis; D000683:Serum Amyloid P-Component / Q000008:administration & dosage* / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000276:immunology; D013131:Spine / Q000276:immunology* / Q000473:pathology; D051193:Toll-Like Receptors / Q000276:immunology; D015854:Up-Regulation; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D000683:Serum Amyloid P-Component; D051193:Toll-Like Receptors; D000099153:Pentraxins
keywords: Experimental autoimmune encephalomyelitis (EAE); Innate immunity; Microglia; Multiple Sclerosis (MS); Pentraxin-3 (PTX3)