Carboxypeptidase B blocks ex vivo activation of the anaphylatoxin-neutrophil extracellular trap axis in neutrophils from COVID-19 patients

• DOI: 10.1186/s13054-021-03482-z
• Publication Date: 2021-02-08T22:44:17Z
• Authors: Yue Zhang; Kai Han; Chunjing Du; Rui Li; Jingyuan Liu; Hui Zeng; Liuluan Zhu; Ang Li
• Keywords: Neutrophil Extracellular Traps; Anaphylatoxin; Proinflammatory cytokine

Abstract Background Thrombosis and coagulopathy are highly prevalent in critically ill patients with COVID-19 increase the risk of death. Immunothrombosis has recently been demonstrated to contribute thrombotic events coagulopathy. As primary components immunothrombosis, neutrophil extracellular traps (NETs) could be induced by complement cascade other proinflammatory mediators. We aimed explore clinical roles NETs regulation on NET formation COVID-19. Methods recruited 135 measured plasma levels C5, C3, cell-free DNA myeloperoxidase (MPO)-DNA. Besides, was detected immunofluorescent staining cytotoxicity vascular endothelial HUVEC cells evaluated CCK-8 assay. Results found that complements C3 MPO-DNA were positively related coagulation indicator fibrin(-ogen) degradation products (C3: r = 0.300, p 0.005; MPO-DNA: 0.316, 0.002) patients. direct bilirubin ( 0.303, 0.004) total 0.304, 0.005), lactate dehydrogenase 0.306, 0.003) creatine kinase 0.308, 0.004). By using anti-C3a anti-C5a antibodies, we revealed component anaphylatoxins strongly formation. The pathological effect anaphylatoxin-NET axis damage relieved recombinant carboxypeptidase B (CPB), a stable homolog enzyme CPB2 which can degrade inactive products. Conclusions Over-activation plays role Early intervention might help prevent thrombosis disease progression