학술논문
Stroke and myocardial infarction induce neutrophil extracellular trap release disrupting lymphoid organ structure and immunoglobulin secretion
Document Type
Original Paper
Author
Tuz, Ali A.; Ghosh, Susmita; Karsch, Laura; Ttoouli, Dimitris; Sata, Sai P.; Ulusoy, Özgür; Kraus, Andreas; Hoerenbaum, Nils; Wolf, Jan-Niklas; Lohmann, Sabrina; Zwirnlein, Franziska; Kaygusuz, Viola; Lakovic, Vivian; Tummes, Hannah-Lea; Beer, Alexander; Gallert, Markus; Thiebes, Stephanie; Qefalia, Altea; Cibir, Zülal; Antler, Medina; Korste, Sebastian; Haj Yehia, Elias; Michel, Lars; Rassaf, Tienush; Kaltwasser, Britta; Abdelrahman, Hossam; Mohamud Yusuf, Ayan; Wang, Chen; Yin, Dongpei; Haeusler, Lars; Lueong, Smiths; Richter, Mathis; Engel, Daniel R.; Stenzel, Martin; Soehnlein, Oliver; Frank, Benedikt; Solo-Nomenjanahary, Mialitiana; Ho-Tin-Noé, Benoît; Siveke, Jens T.; Totzeck, Matthias; Hoffmann, Daniel; Grüneboom, Anika; Hagemann, Nina; Hasenberg, Anja; Desilles, Jean-Philippe; Mazighi, Mikael; Sickmann, Albert; Chen, Jianxu; Hermann, Dirk M.; Gunzer, Matthias; Singh, Vikramjeet
Source
Nature Cardiovascular Research. 3(5):525-540
Subject
Language
English
ISSN
2731-0590
Abstract
Post-injury dysfunction of humoral immunity accounts for infections and poor outcomes in cardiovascular diseases. Among immunoglobulins (Ig), IgA, the most abundant mucosal antibody, is produced by plasma B cells in intestinal Peyer’s patches (PP) and lamina propria. Here we show that patients with stroke and myocardial ischemia (MI) had strongly reduced IgA blood levels. This was phenocopied in experimental mouse models where decreased plasma and fecal IgA were accompanied by rapid loss of IgA-producing plasma cells in PP and lamina propria. Reduced plasma IgG was detectable in patients and experimental mice 3–10 d after injury. Stroke/MI triggered the release of neutrophil extracellular traps (NETs). Depletion of neutrophils, NET degradation or blockade of NET release inhibited the loss of IgA+ cells and circulating IgA in experimental stroke and MI and in patients with stroke. Our results unveil how tissue-injury-triggered systemic NET release disrupts physiological Ig secretion and how this can be inhibited in patients.
Tuz et al. report that stroke and myocardial infarction induce the release of neutrophil extracellular traps (NETs), triggering the loss of B cells and a decrease in immunoglobulin A secretion, and that inhibition of NETs prevents the loss of immunoglobulin A in mice and in patients with stroke.
Tuz et al. report that stroke and myocardial infarction induce the release of neutrophil extracellular traps (NETs), triggering the loss of B cells and a decrease in immunoglobulin A secretion, and that inhibition of NETs prevents the loss of immunoglobulin A in mice and in patients with stroke.