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Lipocalin 2 is a choroid plexus acute-phase protein
Fernanda Marques1, Ana-João Rodrigues, João C Sousa
1Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, Braga, Portugal.
Abstract:
Lipocalin 2 (LCN2) is able to sequester iron-loaded bacterial siderophores and, therefore, is known to participate in the mammalian innate immune response. Of notice, LCN2 was shown to display bacteriostatic effects both in in vitro and in vivo. To reach the brain, bacteria must cross the blood-brain or the choroid plexus (CP)/cerebrospinal fluid (CSF) barriers. Additionally, as the CP is responsible for the production of most of the CSF, responses of the CP mediate signaling into the brain. We show here that in conditions of peripheral inflammation, LCN2 behaves as an acute phase protein in the CP. As early as 1 h after lipopolysaccharide peripheral administration, Lcn2 mRNA levels are upregulated, returning to basal levels after 72 h. Increased LCN2 protein is observed in choroidal epithelia and in endothelial cells of blood vessels in the brain parenchyma. Higher levels of LCN2 are also present in the CSF. These observations suggest that expression of LCN2 at the CP/CSF barrier might be bacteriostatic in the brain, avoiding bacteria dissemination within the CSF into the brain parenchyma. This study shows that the LCN2 is produced by the CP as a component of the innate immune response that protects the central nervous system from infection.
Insights
Lipocalin 2 (LCN2) acts as an acute phase protein in the choroid plexus during inflammation. This innate immune response protein helps protect the central nervous system by preventing bacterial spread in cerebrospinal fluid.
Area of Science:
- Neuroimmunology
- Infectious Disease
Background:
- Lipocalin 2 (LCN2) sequesters bacterial siderophores, contributing to innate immunity with known bacteriostatic effects.
- Bacteria can invade the central nervous system (CNS) via the blood-brain or choroid plexus (CP)/cerebrospinal fluid (CSF) barriers.
- The CP is crucial for CSF production and mediates signaling into the brain.
Purpose of the Study:
- To investigate LCN2's role as an acute phase protein in the CP during peripheral inflammation.
- To determine if LCN2 expression at the CP/CSF barrier impacts bacterial dissemination into the brain.
Main Methods:
- Peripheral administration of lipopolysaccharide (LPS) to induce inflammation.
- Quantitative analysis of Lcn2 mRNA and protein levels in the CP, brain parenchyma, and CSF.
- Assessment of LCN2 localization in choroidal epithelia and brain vasculature.
Main Results:
- Lcn2 mRNA levels significantly upregulated in the CP within 1 hour of LPS administration, returning to baseline by 72 hours.
- Increased LCN2 protein detected in choroidal epithelia and brain blood vessel endothelial cells.
- Elevated LCN2 levels observed in the cerebrospinal fluid.
Conclusions:
- LCN2 functions as an acute phase protein in the CP during systemic inflammation.
- LCN2 expression at the CP/CSF barrier may provide a bacteriostatic defense, limiting bacterial spread into the CNS.
- The CP produces LCN2 as part of the innate immune system's defense of the central nervous system against infection.
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