Corticosteroid-binding globulin (CBG) is a 50-60 kDa circulating glycoprotein with high affinity for cortisol. CBG is adapted for sepsis; its cortisol binding is reduced reversibly by pyrexia and acidaemia, and reduced irreversibly by neutrophil elastase (NE) cleavage, converting high cortisol-binding affinity CBG to a low affinity form. These characteristics allow for the targeted delivery of immunomodulatory cortisol to tissues at the time and body site where cortisol is required in sepsis and septic shock. In addition, high titer inflammatory cytokines in sepsis suppress CBG hepatic synthesis, increasing the serum free cortisol fraction. Recent clinical studies have highlighted the importance of CBG in septic shock, with CBG deficiency independently associated with mortality.
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Mass spectrometric detection of neutrophil elastase cleaved corticosteroid binding globulin and its association with Asn347 site glycosylation, in septic shock patients.
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Department of Medicine, University of Adelaide, Australia; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Australia; Endocrine and Diabetes Services, The Queen Elizabeth Hospital, Australia.
Background: Corticosteroid-binding globulin (CBG) modulates tissue cortisol availability via modification of cortisol:CBG binding affinity in response to multiple factors, including neutrophil elastase (NE) cleavage of the reactive centre loop (RCL), converting high affinity CBG (haCBG) to low affinity CBG (laCBG). In vitro, glycosylation of the RCL at Asn347 affects NE cleavage susceptibility. To date, no direct measurement of laCBG, which would verify NE cleavage, has been reported.
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