Proteolytic inactivation of CXCL12 in the lungs and circulation of COVID-19 patients
Cell Mol Life Sci. 2023 Jul 28;80(8):234. doi: 10.1007/s00018-023-04870-0.ABSTRACTThe human chemokine stromal cell-derived factor-1 (SDF-1) or CXCL12 is involved in several homeostatic processes and pathologies through interaction with its cognate G protein-coupled receptor CXCR4. Recent research has shown that CXCL12 is present in the lungs and circulation of patients with coronavirus disease 2019 (COVID-19). However, the question whether the detected CXCL12 is bioactive was not addressed. Indeed, the activity of CXCL12 is regulated by NH2- and COOH-terminal post-translational proteolysis, which significantly impairs its biological activity. The aim of the present study was to characterize proteolytic processing of CXCL12 in broncho-alveolar lavage (BAL) fluid and blood plasma samples from critically ill COVID-19 patients. Therefore, we optimized immunosorbent tandem mass spectrometry proteoform analysis (ISTAMPA) for detection of CXCL12 proteoforms. In patient samples, this approach uncovered that CXCL12 is rapidly processed by site-specific NH2- and COOH-terminal proteolysis and ultimately degraded. This proteolytic inactivation occurred more rapidly in COVID-19 plasma than in COVID-19 BAL fluids, whereas BAL fluid samples from stable lung transplantation patients and the non-affected lung of lung cancer patients (control groups) hardly induced any processing of CXCL12. In COVID-19 BAL fluids with high proteolytic activity, processing occurred exclusively NH2-terminally an...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Seppe Cambier Fabio Beretta No ëmie Pörtner Mieke Metzemaekers Ana Carolina de Carvalho Erik Martens Janne Kaes Celine Aelbrecht Cato Jacobs Pierre Van Mol Els Wauters Philippe Meersseman Greet Hermans Rafael Elias Marques Bart Vanaudenaerde Robin Vos J Source Type: research
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