Stroke and myocardial infarction induce neutrophil extracellular trap release disrupting lymphoid organ structure and immunoglobulin secretion.

Stroke and myocardial infarction induce neutrophil extracellular trap release disrupting lymphoid organ structure and immunoglobulin secretion.

Nature cardiovascular research (2024-08-28)

Ali A Tuz, Susmita Ghosh, Laura Karsch, Dimitris Ttoouli, Sai P Sata, Özgür Ulusoy, Andreas Kraus, Nils Hoerenbaum, Jan-Niklas Wolf, Sabrina Lohmann, Franziska Zwirnlein, Viola Kaygusuz, Vivian Lakovic, Hannah-Lea Tummes, Alexander Beer, Markus Gallert, Stephanie Thiebes, Altea Qefalia, Zülal Cibir, Medina Antler, Sebastian Korste, Elias Haj Yehia, Lars Michel, Tienush Rassaf, Britta Kaltwasser, Hossam Abdelrahman, Ayan Mohamud Yusuf, Chen Wang, Dongpei Yin, Lars Haeusler, Smiths Lueong, Mathis Richter, Daniel R Engel, Martin Stenzel, Oliver Soehnlein, Benedikt Frank, Mialitiana Solo-Nomenjanahary, Benoît Ho-Tin-Noé, Jens T Siveke, Matthias Totzeck, Daniel Hoffmann, Anika Grüneboom, Nina Hagemann, Anja Hasenberg, Jean-Philippe Desilles, Mikael Mazighi, Albert Sickmann, Jianxu Chen, Dirk M Hermann, Matthias Gunzer, Vikramjeet Singh

PMID39195931

ZUSAMMENFASSUNG

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.

MATERIALIEN

Produktnummer

Marke

Produktbeschreibung

506282

Sigma-Aldrich

PAD-Inhibitor, Cl-Amidin, Cl-amidine is a cell-permeable pan PAD inhibitor (IC₅₀ = 0.8, 6.2, and 5.9 µM for PAD1, PAD3, and PAD4, respectively). Inactivates the calcium bound form of PAD4 in an irreversible manner.