Formyl peptide chemoattractant receptors in leukocyte activation and trans-endothelial migration

    Formyl Peptide Receptors (FPRs) recognize and react to a broad range of diverse pathogen-associated molecules and endogenous ligands including proinflammatory mitochondrial peptides and the anti-inflammatory Annexin I (AnxA1). In order to understand how FPRs are capable of triggering different pathways that govern contrasting responses (“biased agonism”), we will analyze agonist-specific FPR signaling fingerprints, as well as the dynamics of FPR-containing supramolecular complexes. AnxA1 is secreted from cells by unconventional mechanisms. We will characterize endothelial plasma membrane wounds inflicted by dynamic leukocyte-endothelial cell interactions and analyze the repair machinery as a potential mechanism of AnxA1 release.

    Research area: Leukocyte biology, endothelial cell biology

    Prof. Dr. rer.nat. Ursula Rescher
    Prof. Dr. rer. nat. Volker Gerke

    Funding period: July 2012 - June 2024

    • Publications

      Original articles

      • Ashraf A, Gerke V (2021) Plasma membrane wound repair is characterized by extensive membrane lipid and protein rearrangements in vascular endothelial cells. BBA Mol Cell Res 1868: 118991
      • Holthenrich A, Drexler HCA, Chehab T, Naß J, Gerke V (2019) Proximity proteomics of endothelial Weibel-Palade bodies identifies novel regulator of von-Willebrand factor secretion. Blood 134: 979-982.
      • Schloer S, Hübel N, Masemann D, Pajonczyk D, Brunotte L, Ehrhardt C, Brandenburg LO, Ludwig S, Gerke V, Rescher U (2019a) The annexin A1/FPR2 signaling axis expands alveolar macrophages, limits viral replication, and attenuates pathogenesis in the murina influenza A virus infection model. FASEB J 33(11):12188-12199. doi: 10.1096/fj.201901265R.
      • Schloer S, Goretzko J, Kuehnl A, Brunotte L, Ludwig S, Rescher U (2019b) The clinically licensed antifungal drug itraconazole inhibits influenza virus in vitro and in vivo. Emerg Microbes Infect 8: 80-93.
      • Krischuns T, Günl F, Henschel L, Binder M, Willemsen J, Schloer S, Rescher U, Gerlt V, Zimmer G, Nordhoff C, Ludwig S, Brunotte L (2018) Phosphorylation of TRIM28 Enhances the Expression of IFN-beta and Proinflammatory Cytokines During HPAIV Infection of Human Lung Epithelial Cells. Front Immunol 9: 2229.
      • Kühnl A, Musiol A, Heitzig N, Johnson DE, Ehrhardt C, Grewal T, Gerke V, Ludwig S, Rescher U (2018) Late endosomal/lysosomal cholesterol accumulation is a host cell-protective mechanism inhibiting endosomal escape of influenza A virus. mBio 9: pii:e01345-18.
      • Boye LT, Maeda K, Pezeshkian W, Sønder LS, Hager CS, Gerke V, Simonsen AC, Nylandsted J (2017). Annexin A4 and A6 induce membrane curvature and constriction during cell membrane repair. Nat Commun 8: 1623.
      • Heitzig N, Brinkmann BF, Koerdt SN, Rosso G, Shahin V, Rescher U (2017). Annexin A8 promotes VEGF-A driven endothelial cell sprouting. Cell Adh Migr. 11: 275-287.
      • Heitzig N, Kühnl A, Grill D, Ludewig K, Schloer S, Galla HJ, Grewal T, Gerke V, Rescher U (2018). Cooperative binding promotes demand-driven recruitment of AnxA8 to cholesterol containing membranes. BBA Mol Cell Biol Lipids 1863: 349-358.
      • Koerdt S, Gerke V (2017). Annexin A2 is involved in Ca2+-dependent plasma membrane repair in primary human endothelial cells. BBA Mol Cell Res 1864: 1046-1053.
      • Lueck K, Carr A-J F, Stampoulis D, Gerke V, Rescher U, Greenwood J & Moss S E (2017). Regulation of retinal pigment epithelial cell phenotype by Annexin A8. Scientific Reports, 7, 4638. (
      • Poeter M, Brandherm I, Rossaint J, Rosso G, Shahin V, Skryabin BV, Zabock A, Gerke V, Rescher U (2014) Annexin A8 controls leucocyte recruitment to activated endothelial cells via cells surface delivery of CD63. Nature Commun 5: 3738. (doi: 10.1038/ncomms4738, 28 April 2014-06-05)
      • Ghavampour S, Lange C, Bottino C, Gerke V (2013) Transcriptional profiling of human monocytes identifies the inhibitory receptor CD300a as regulator of transendothelial migration. PLOS One 8 (9): e73981.
      • Musiol A, Gran S, Ehrhardt C, Ludwig S, Grewal T, Gerke V, Rescher U (2013) Annexin A6-balanced late endosomal cholesterol controls Influenza A replication and propagation.MBio 4(6): e00608-13. (doi: 10.1128/mBio.00608-13


      • Raabe C, Gröper J, Rescher U (2019). Biased perspectives on formyl peptide receptors. BBA Mol Cell Res 1866: 305-316.