Rituximab induces a flare-up of activated neutrophil extracellular traps under in vitro conditions. (2nd November 2022)

• Record Type: Journal Article
• Authors: Hoffmann, Joerg; Roesner, Samira; Neubauer, Andreas
• Is Part Of: Immunopharmacology and immunotoxicology. Volume 44:Number 6(2022)
• Page Start: 860
• Page End: 867
• Publication Date: 2022-11-02
• Subjects: Neutrophil extracellular traps -- inflammation -- Rituximab -- acetylsalicylic acid -- aspirin -- NET formation -- flow cytometry; Immunopharmacology -- Periodicals; Immunotoxicology -- Periodicals; Antibody-toxin conjugates -- Periodicals; Immunology -- Periodicals; 615.37
• DOI: 10.1080/08923973.2022.2088386
• Languages: English
• ISSNs: 0892-3973

Abstract

Abstract: Purpose: During neutrophil extracellular traps (NET) formation granulocytes release a decondensed chromatin web that is studded with antimicrobial proteins. These NET engulf and kill pathogens like bacteria and fungi. NET formation is part of the innate immune response but can also contribute to the aggravation of autoimmune diseases, thrombosis, and cancer metastasis. Anti-NET therapeutics to prevent potentially harmful consequences of excessive NET formation are warranted. Materials and methods: Therefore, we stimulated NET formation with ionomycin in the peripheral blood of 25 healthy individuals and quantified NET with flow cytometry and fluorescence microscopy after exposure to five different anti-inflammatory and cytostatic drugs. NET were identified by their expression of myeloperoxidase, citrullinated histone H3, and (extracellular) DNA release. Results: The preliminary in vitro drug screening indicated that acetylsalicylic acid (ASA) might suppress (−3.82%), and rituximab might enhance (+10.52%) NET formation. To consolidate the screening results, we quantified NET after exposure to rituximab and ASA in the blood of nine additional healthy subjects. Rituximab showed a significant increased NET formation compared to the neutrophils treated with ASA (a mean of differences 3.96%; 95% CI 1.90–6.03%; p < .01) or compared to neutrophils without treatment (a mean of differences 4.39%; 95% CI 1.17–7.61%; p = .01). Contrary to the screening results ASA showed no significant suppression of NET formation in the consolidation experiments (a mean of differences 0.43%; 95% CI −1.27 to 2.12%; p = .58). Conclusions: We conclude that rituximab therapy might further trigger activated NET formation and should be applied with caution in patients with pro-inflammatory state and underlying autoimmune disease, thrombosis, or cancer.