Hypogelsolinemia, a disorder of the extracellular actin scavenger system, in patients with multiple sclerosis

Alina Kułakowska,Maciej Szmitkowski,Paul A Janmey,Wiesław Drozdowski,Robert Bucki,Qi Wen,Nicholas J Ciccarelli,Barbara Mroczko

doi:10.1186/1471-2377-10-107

Alina Kułakowska, Maciej Szmitkowski + Show 6 more

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https://doi.org/10.1186/1471-2377-10-107

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BackgroundExtracellular gelsolin (GSN) and GC-globulin/Vitamin D-binding protein (DBP) appear to play an important role in clearing the actin from extracellular fluids and in modulating cellular responses to anionic bioactive lipids. In this study we hypothesized that cellular actin release and/or increase in bioactive lipids associated with multiple sclerosis (MS) development will translate into alteration of the actin scavenger system protein concentrations in blood and cerebrospinal fluid (CSF) of patients with MS.MethodsWe measured GSN and DBP concentrations in blood and CSF obtained from patients diagnosed with MS (n = 56) in comparison to a control group (n = 20) that includes patients diagnosed with conditions such as idiopathic cephalgia (n = 11), idiopathic (Bell's) facial nerve palsy (n = 7) and ischialgia due to discopathy (n = 2). GSN and DBP levels were measured by Western blot and ELISA, respectively.ResultsWe found that the GSN concentration in the blood of the MS group (115 ± 78 μg/ml) was significantly lower (p < 0.001) compared to the control group (244 ± 96 μg/ml). In contrast, there was no statistically significant difference between blood DBP concentrations in patients with MS (310 ± 68 μg/ml) and the control group (314 ± 82 μg/ml). GSN and DBP concentrations in CSF also did not significantly differ between those two groups.ConclusionsThe decrease of GSN concentration in blood and CSF of MS subjects suggests that this protein may be involved in chronic inflammation associated with neurodegeneration. Additionally, the results presented here suggest the possible utility of GSN evaluation for diagnostic purposes. Reversing plasma GSN deficiency might represent a new strategy in MS treatment.

Highlights

Extracellular gelsolin (GSN) and GC-globulin/Vitamin D-binding protein (DBP) appear to play an important role in clearing the actin from extracellular fluids and in modulating cellular responses to anionic bioactive lipids
There was no significant difference between DBP levels in blood of multiple sclerosis (MS) patients and the control group (310 ± 68 μg/ml versus 314 ± 82), determined using ELISA
As all patients included in MS group were suffering from the relapsing-remitting form of the disease at early stages (Table 1), it may be concluded that depletion of plasma gelsolin represents an early event during MS development

Summary

Introduction

Extracellular gelsolin (GSN) and GC-globulin/Vitamin D-binding protein (DBP) appear to play an important role in clearing the actin from extracellular fluids and in modulating cellular responses to anionic bioactive lipids. Low DBP levels (both the total level and the actin-free level, which is an index of residual actin-scavenging capacity), was proposed to serve as a prognostic marker in situations of organ damage such as acute liver failure, and multiple trauma [18]. Other conditions such as septic shock may be associated with reduced DBP levels and complex formation with actin [19]. Gelsolin’s interaction with bioactive lipids can alter its ability to bind actin [24]

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