title: Lipocalin 2 plays an immunomodulatory role and has detrimental effects after spinal cord injury.
abstract: Lipocalin 2 (Lcn2) plays an important role in defense against bacterial infection by interfering with bacterial iron acquisition. Although Lcn2 is expressed in a number of aseptic inflammatory conditions, its role in these conditions remains unclear. We examined the expression and role of Lcn2 after spinal cord injury (SCI) in adult mice by using a contusion injury model. Lcn2 expression at the protein level is rapidly increased 12-fold at 1 d after SCI and decreases gradually thereafter, being three times as high as control levels at 21 d after injury. Lcn2 expression is strongly induced after contusion injury in astrocytes, neurons, and neutrophils. The Lcn2 receptor (Lcn2R), which has been shown to influence cell survival, is also expressed after SCI in the same cell types. Lcn2-deficient (Lcn2⁻/⁻) mice showed significantly better locomotor recovery after spinal cord contusion injury than wild-type (Lcn2⁺/⁺) mice. Histological assessments indicate improved neuronal and tissue survival and greater sparing of myelin in Lcn2⁻/⁻ mice after contusion injury. Flow cytometry showed a decrease in neutrophil influx and a small increase in the monocyte population in Lcn2⁻/⁻ injured spinal cords. This change was accompanied by a reduction in the expression of several pro-inflammatory chemokines and cytokines as well as inducible nitric oxide synthase early after SCI in Lcn2⁻/⁻ mice compared with wild-type animals. Our results, therefore, suggest a role for Lcn2 in regulating inflammation in the injured spinal cord and that lack of Lcn2 reduces secondary damage and improves locomotor recovery after spinal cord contusion injury.
authors.affiliation: Center for Research in Neuroscience, The Research Institute of the McGill University Health Center, Montreal, Quebec H3G1A4, Canada.
authors.forename: Khizr I
authors.initials: KI
authors.lastname: Rathore
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Berard
authors.forename: Adriana
authors.initials: A
authors.lastname: Redensek
authors.forename: Sabrina
authors.initials: S
authors.lastname: Chierzi
authors.forename: Ruben
authors.initials: R
authors.lastname: Lopez-Vales
authors.forename: Manuela
authors.initials: M
authors.lastname: Santos
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Samuel
authors.initials: S
authors.lastname: David
mesh_terms: D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002470:Cell Survival / Q000235:genetics / Q000502:physiology*; D003711:Demyelinating Diseases / Q000235:genetics / Q000503:physiopathology; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D020127:Recovery of Function / Q000235:genetics / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000209:Acute-Phase Proteins; D018836:Inflammation Mediators; D000071068:Lipocalin-2; D054834:Lipocalins; D052247:Nitric Oxide Synthase Type II; D015513:Oncogene Proteins; D011956:Receptors, Cell Surface; C508313:Slc22a17 protein, mouse; C071332:Lcn2 protein, mouse