Role of α-actinin in neutrophil recruitment and neutrophil effector function
In order to leave the vessel at sites of tissue damage and inflammation, leukocytes have to interact with the endothelium prior transmigration into inflamed tissues. Integrins are required for leukocyte recruitment and functions and the actin cytoskeleton plays a central role in immune cell formation and function. The F-actin-binding proteins talin, α-actinin, and filamin bind integrin cytoplasmic tails as well as other cytoskeletal or scaffold proteins, and mediate the attachment of integrins to actin filaments. However, the complex mechanisms underlying integrin–cytoskeletal linkage regulation remain to be elucidated. α-Actinins (ACTN) are actin filament crosslinking proteins and leukocytes exclusively express ACTN1 and 4. We specifically investigate the role of ACTN1 in integrin activation and neutrophil activation and function. We investigate the role of ACTN1 in inflammation in clinically relevant disease models and how ACTN1 in neutrophils is involved in integrin activation and neutrophil recruitment. Furthermore, we study if ACTN1 is also involved in neutrophil antimicrobial effector functions mediated by integrin outside-in signalling.
Team
Publications
Integrin Activation by Two Independently Regulated Calcium-Mediated Pathways Is Required for Neutrophil RecruitmentOguama, M.; Lindental, P.; Clemens, R. A.; Lowell, C. A.; Soehnlein, O.; Roth, J.; Bakchoul, T.; Cappenberg, A.; Zarbock, A.
2026 Cell Commun Signal
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The Nuclear Receptor NR4A1 Serves as a Neutrophil-Intrinsic Regulator Mitigating Stroke SeverityStrecker, J.-K.; Schmidt, Y.; Liebmann, M.; Walter, C.; Roth, S.; Aleth, H.; Börsch, A.-L.; Schmidt-Pogoda, A.; Beuker, C.; Yusuf, A. M.; Revenstorff, J.; Osei-Sarpong, C.; Krafft, L.; Schwarze, A.-S.; Heming, M.; Richter, M.; Kuhlmann, T.; Hucke, S.; Heming, J.-N.; Hansen, U.; Hagemann, N.; Bader, A.; Gao, J.; Walzog, B.; Maier-Begandt, D.; Chevre, R.; Hanschmann, E.-M.; Lücke, M.; Sommer, C.; Hermann, D. M.; Roth, J.; Thomas, C.; Meyer Zu Hörste, G.; Gunzer, M.; Vogl, T.; Zarbock, A.; Rosenbauer, F.; Silvestre-Roig, C.; Söhnlein, O.; Klotz, L.; Minnerup, J.
2025 bioRxiv
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Neutrophil Progenitor Mobilization Is a Distinct Feature of STEMI and Predicts SurvivalRichter, M.; Von Göwels*, J.; Fähndrich*, M.; Fernandez*, C. L.; Grohn*, K.; Schwarz, D.; Lang, A.; Polzin, A.; Farinola, L.; Gosh, S.; Groba, S. R.; Heming, J.-N.; Aleth, H.; Rübsamen, N.; Radecke, T.; Rosenbauer, F.; Sickmann, A.; Karch, A.; Zarbock, A.; Minnerup, J.; Sindermann, J.; Bender, A.; Rossaint, J.; Ormanns, S.; Gunzer, M.; Reinecke, H.; Makowski, L.; Jung, C.; Silvestre-Roig, C.; Kelm, M.; Gerdes, N.; Chevre, R.; Lange, S.; Soehnlein, O.
2025 Research Square
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CD45 and CD148 Are Critically Involved in Neutrophil Recruitment and Function During Inflammatory Arthritis in MiceHeming, J.-N.; Margraf, A.; Najder, K.; Germena, G.; Richter, M.; Cappenberg, A.; Henke, K.; Bardel, B.; Schemmelmann, L.; Oguama, M.; Lindental, P.; Amini, W.; Sobocik, J.; Schett, G.; Krönke, G.; Block, H.; Rossaint, J.; Soehnlein, O.; Zarbock, A.
2025 Cells
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RhoA GAP Myo9b Regulates Β2-Integrin Activity and Neutrophil Recruitment during Murine Acute Kidney InjuryCappenberg, A.; Oguama, M.; Richter, M.; Margraf, A.; Amini, W.; Lindental, P.; Mersmann, S.; Bardel, B.; Block, H.; Vogl, T.; Soehnlein, O.; Ley, K.; Rossaint, J.; Zarbock, A.
2025 Blood
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Csk-Mediated Src Family Kinase Regulation Dampens Neutrophil Infiltration during Pulmonary InfectionAmini, W.; Schemmelmann, L.; Heming, J.-N.; Oguama, M.; Thomas, K.; Block, H.; Lindental, P.; Bardel, B.; Margraf, A.; Soehnlein, O.; Cappenberg, A.; Zarbock, A.
2025 JCI Insight
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Alveolar Epithelial and Vascular CXCR2 Mediates Transcytosis of CXCL1 in Inflamed LungsThomas, K.; Rossaint, J.; Ludwig, N.; Mersmann, S.; Kötting, N.; Grenzheuser, J.; Schemmelmann, L.; Oguama, M.; Margraf, A.; Block, H.; Henke, K.; Hellenthal, K.; Mirakaj, V.; Gerke, V.; Hansen, U.; Gäher, K.; Engelhardt, M.; Roth, J.; Eble, J.; Hub, E.; Rot, A.; Alon, R.; Zarbock, A.
2025 Nat Commun
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Glutamine Modulates Neutrophil Recruitment and Effector Functions during Sterile InflammationHellenthal, K. E. M.; Thomas, K.; Ludwig, N.; Cappenberg, A.; Schemmelmann, L.; Tekath, T.; Margraf, A.; Mersmann, S.; Henke, K.; Rossaint, J.; Zarbock, A.; Amini, W.
2024 J Leukoc Biol
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Neutrophils - Biology and DiversityMaier-Begandt, D.; Alonso-Gonzalez, N.; Klotz, L.; Erpenbeck, L.; Jablonska, J.; Immler, R.; Hasenberg, A.; Mueller, T. T.; Herrero-Cervera, A.; Aranda-Pardos, I.; Flora, K.; Zarbock, A.; Brandau, S.; Schulz, C.; Soehnlein, O.; Steiger, S.; the TRR332 consortium.
2023 Nephrol Dial Transplant
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Nuclease Activity and Protein A Release of Staphylococcus Aureus Clinical Isolates Determine the Virulence in a Murine Model of Acute Lung Infection.Ludwig, N.; Thörner-van Almsick, J.; Mersmann, S.; Bardel, B.; Niemann, S.; Chasan, A. I.; Schäfers, M.; Margraf, A.; Rossaint, J.; Kahl, B. C.; Zarbock, A.; Block, H.
2023 Front Immunol
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Glutamine Prevents Acute Kidney Injury by Modulating Oxidative Stress and Apoptosis in Tubular Epithelial CellsThomas, K.; Zondler, L.; Ludwig, N.; Kardell, M.; Lüneburg, C.; Henke, K.; Mersmann, S.; Margraf, A.; Spieker, T.; Tekath, T.; Velic, A.; Holtmeier, R.; Hermann, J.; Jankowski, V.; Meersch, M.; Vestweber, D.; Westphal, M.; Roth, J.; Schäfers, M. A.; Kellum, J. A.; Lowell, C. A.; Rossaint, J.; Zarbock, A.
2022 JCI Insight
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