Human platelet concentrates

A source of solvent/detergent-treated highly enriched brain-derived neurotrophic factor

Thierry Burnouf, Ya Po Kuo, David Blum, Sylvie Burnouf, Chen Yao Su

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: Human blood platelets (PLTs) contain brain-derived neurotrophic factor (BDNF), a neurotrophin that binds to neurotrophic tropomyosin-related kinase B (TrkB) receptor on central nervous system cells. This binding promotes neural synaptic plasticity and memory and prevents neuronal degeneration. Alterations in BDNF homeostasis are associated with aging and are found in several neurodegenerative conditions such as Alzheimer's, Huntington's, and Parkinson's diseases and multiple sclerosis. We have developed PLT viral inactivation and chromatographic fractionation processes and decided here to identify fractions enriched in BDNF. Study Design and Methods: PLT concentrates (PCs) were treated by solvent/detergent (S/D), extracted by oil, and subjected to fractionation (C18, sulfopropyl [SP]-Sepharose, diethylaminoethyl [DEAE]-Sepharose, or activated charcoal). BDNF and pro-BDNF were evaluated by enzyme-linked immunosorbent assay, and Western blot. TrkB was studied by Western blot. Tri-n-butyl phosphate (TnBP) was quantified by high-performance liquid chromatography, and Triton X-45 by gas chromatography. Results: The mean BDNF content of 2.9 ± 0.7 ng/mL in PC was noted to increase to 56.2 ± 2.4 ng/mL after S/D treatment and remained stable during oil extraction. Approximately 70% of the BDNF content was recovered after C18 chromatography. BDNF did not bind to DEAE-Sepharose and was almost completely adsorbed by charcoal. Chromatography on SP-Sepharose yielded a highly enriched 13-kDa mature BDNF fraction that was more than 170-fold purified, with a mean of 137 ± 29.4 ng/mL and 82% chromatographic recovery, devoid of detectable TnBP and Triton X-45. Pro-BDNF and TrkB proteins were not detected in the PLT extracts. Conclusion: We obtained a S/D-treated, highly enriched mature PLT-derived BDNF fraction that could help unveil the pharmacokinetics, pharmacodynamic, and potential therapeutic applications of the BDNF neurotrophin.

Original languageEnglish
Pages (from-to)1721-1728
Number of pages8
JournalTransfusion
Volume52
Issue number8
DOIs
Publication statusPublished - Aug 2012

Fingerprint

Brain-Derived Neurotrophic Factor
Detergents
Blood Platelets
Sepharose
Neuronal Plasticity
Charcoal
Octoxynol
Nerve Growth Factors
Chromatography
Oils
Western Blotting
Virus Inactivation
Huntington Disease
Gas Chromatography
Multiple Sclerosis
Parkinson Disease
Alzheimer Disease
Homeostasis
Central Nervous System
Pharmacokinetics

ASJC Scopus subject areas

  • Hematology
  • Immunology
  • Immunology and Allergy

Cite this

Human platelet concentrates : A source of solvent/detergent-treated highly enriched brain-derived neurotrophic factor. / Burnouf, Thierry; Kuo, Ya Po; Blum, David; Burnouf, Sylvie; Su, Chen Yao.

In: Transfusion, Vol. 52, No. 8, 08.2012, p. 1721-1728.

Research output: Contribution to journalArticle

Burnouf, Thierry ; Kuo, Ya Po ; Blum, David ; Burnouf, Sylvie ; Su, Chen Yao. / Human platelet concentrates : A source of solvent/detergent-treated highly enriched brain-derived neurotrophic factor. In: Transfusion. 2012 ; Vol. 52, No. 8. pp. 1721-1728.
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abstract = "Background: Human blood platelets (PLTs) contain brain-derived neurotrophic factor (BDNF), a neurotrophin that binds to neurotrophic tropomyosin-related kinase B (TrkB) receptor on central nervous system cells. This binding promotes neural synaptic plasticity and memory and prevents neuronal degeneration. Alterations in BDNF homeostasis are associated with aging and are found in several neurodegenerative conditions such as Alzheimer's, Huntington's, and Parkinson's diseases and multiple sclerosis. We have developed PLT viral inactivation and chromatographic fractionation processes and decided here to identify fractions enriched in BDNF. Study Design and Methods: PLT concentrates (PCs) were treated by solvent/detergent (S/D), extracted by oil, and subjected to fractionation (C18, sulfopropyl [SP]-Sepharose, diethylaminoethyl [DEAE]-Sepharose, or activated charcoal). BDNF and pro-BDNF were evaluated by enzyme-linked immunosorbent assay, and Western blot. TrkB was studied by Western blot. Tri-n-butyl phosphate (TnBP) was quantified by high-performance liquid chromatography, and Triton X-45 by gas chromatography. Results: The mean BDNF content of 2.9 ± 0.7 ng/mL in PC was noted to increase to 56.2 ± 2.4 ng/mL after S/D treatment and remained stable during oil extraction. Approximately 70{\%} of the BDNF content was recovered after C18 chromatography. BDNF did not bind to DEAE-Sepharose and was almost completely adsorbed by charcoal. Chromatography on SP-Sepharose yielded a highly enriched 13-kDa mature BDNF fraction that was more than 170-fold purified, with a mean of 137 ± 29.4 ng/mL and 82{\%} chromatographic recovery, devoid of detectable TnBP and Triton X-45. Pro-BDNF and TrkB proteins were not detected in the PLT extracts. Conclusion: We obtained a S/D-treated, highly enriched mature PLT-derived BDNF fraction that could help unveil the pharmacokinetics, pharmacodynamic, and potential therapeutic applications of the BDNF neurotrophin.",
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