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Sensitive mass spectrometric determination of kinin-kallikrein system peptides in light of COVID-19.
Gangnus, Tanja; Burckhardt, Bjoern B.
  • Gangnus T; Institute of Clinical Pharmacy and Pharmacotherapy, Heinrich Heine University, Universitaetsstr. 1, 40225, Düsseldorf, Germany.
  • Burckhardt BB; Institute of Clinical Pharmacy and Pharmacotherapy, Heinrich Heine University, Universitaetsstr. 1, 40225, Düsseldorf, Germany. bjoern.burckhardt@hhu.de.
Sci Rep ; 11(1): 3061, 2021 02 04.
Article in English | MEDLINE | ID: covidwho-1065953
ABSTRACT
The outbreak of COVID-19 has raised interest in the kinin-kallikrein system. Viral blockade of the angiotensin-converting enzyme 2 impedes degradation of the active kinin des-Arg(9)-bradykinin, which thus increasingly activates bradykinin receptors known to promote inflammation, cough, and edema-symptoms that are commonly observed in COVID-19. However, lean and reliable investigation of the postulated alterations is currently hindered by non-specific peptide adsorption, lacking sensitivity, and cross-reactivity of applicable assays. Here, an LC-MS/MS method was established to determine the following kinins in respiratory lavage fluids kallidin, bradykinin, des-Arg(10)-kallidin, des-Arg(9)-bradykinin, bradykinin 1-7, bradykinin 2-9 and bradykinin 1-5. This method was fully validated according to regulatory bioanalytical guidelines of the European Medicine Agency and the US Food and Drug Administration and has a broad calibration curve range (up to a factor of 103), encompassing low quantification limits of 4.4-22.8 pg/mL (depending on the individual kinin). The application of the developed LC-MS/MS method to nasal lavage fluid allowed for the rapid (~ 2 h), comprehensive and low-volume (100 µL) determination of kinins. Hence, this novel assay may support current efforts to investigate the pathophysiology of COVID-19, but can also be extended to other diseases.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Bradykinin / Kallikrein-Kinin System / Nasal Lavage Fluid Type of study: Prognostic study / Randomized controlled trials Limits: Adult / Female / Humans / Male / Young adult Language: English Journal: Sci Rep Year: 2021 Document Type: Article Affiliation country: S41598-021-82191-7

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Bradykinin / Kallikrein-Kinin System / Nasal Lavage Fluid Type of study: Prognostic study / Randomized controlled trials Limits: Adult / Female / Humans / Male / Young adult Language: English Journal: Sci Rep Year: 2021 Document Type: Article Affiliation country: S41598-021-82191-7