Your browser doesn't support javascript.
loading
Neutrophil elastase-cleaved corticosteroid-binding globulin is absent in human plasma.
Hill, Lesley A; Vassiliadi, Dimitra A; Dimopoulou, Ioanna; Anderson, Anna J; Boyle, Luke D; Kilgour, Alixe H M; Stimson, Roland H; Machado, Yoan; Overall, Christopher M; Walker, Brian R; Lewis, John G; Hammond, Geoffrey L.
Afiliación
  • Hill LA; Departments of Cellular and Physiological Sciences and Obstetrics and Gynaecology, The University of British Columbia, Vancouver, British Columbia, Canada.
  • Vassiliadi DA; Endocrine Unit, Second Department of Internal Medicine-Research Institute and Diabetes Center, Attiko University Hospital, Athens, Greece.
  • Dimopoulou I; Endocrine Unit, Second Department of Internal Medicine-Research Institute and Diabetes Center, Attiko University Hospital, Athens, Greece.
  • Anderson AJ; BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
  • Boyle LD; BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
  • Kilgour AHM; BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
  • Stimson RH; BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
  • Machado Y; Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, British Columbia, Canada.
  • Overall CM; Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, British Columbia, Canada.
  • Walker BR; BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
  • Lewis JG; Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
  • Hammond GL; Canterbury Health Laboratories, Christchurch, New Zealand.
J Endocrinol ; 240(1): 27-39, 2019 01 01.
Article en En | MEDLINE | ID: mdl-30452386
Corticosteroid-binding globulin (CBG) transports glucocorticoids in blood and is a serine protease inhibitor family member. Human CBG has a reactive center loop (RCL) which, when cleaved by neutrophil elastase (NE), disrupts its steroid-binding activity. Measurements of CBG levels are typically based on steroid-binding capacity or immunoassays. Discrepancies in ELISAs using monoclonal antibodies that discriminate between intact vs RCL-cleaved CBG have been interpreted as evidence that CBG with a cleaved RCL and low affinity for cortisol exists in the circulation. We examined the biochemical properties of plasma CBG in samples with discordant ELISA measurements and sought to identify RCL-cleaved CBG in human blood samples. Plasma CBG-binding capacity and ELISA values were consistent in arterial and venous blood draining skeletal muscle, liver and brain, as well as from a tissue (adipose) expected to contain activated neutrophils in obese individuals. Moreover, RCL-cleaved CBG was undetectable in plasma from critically ill patients, irrespective of whether their ELISA measurements were concordant or discordant. We found no evidence of RCL-cleaved CBG in plasma using a heat-dependent polymerization assay, and CBG that resists immunoprecipitation with a monoclonal antibody designed to specifically recognize an intact RCL, bound steroids with a high affinity. In addition, mass spectrometry confirmed the absence of NE-cleaved CBG in plasma in which ELISA values were highly discordant. Human CBG with a NE-cleaved RCL and low affinity for steroids is absent in blood samples, and CBG ELISA discrepancies likely reflect structural differences that alter epitopes recognized by specific monoclonal antibodies.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esteroides / Transcortina / Hidrocortisona / Elastasa de Leucocito Límite: Adult / Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: J Endocrinol Año: 2019 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esteroides / Transcortina / Hidrocortisona / Elastasa de Leucocito Límite: Adult / Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: J Endocrinol Año: 2019 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido