[{"ddc":["570"],"page":"902 - 909","quality_controlled":"1","publisher":"Cell Press","article_processing_charge":"Yes","doi":"10.1016/j.celrep.2017.04.027","type":"journal_article","_id":"672","date_updated":"2023-02-23T12:50:09Z","status":"public","publication":"Cell Reports","project":[{"_id":"25A603A2-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)","grant_number":"281556"},{"call_identifier":"FWF","name":"Cytoskeletal force generation and transduction of leukocytes (FWF)","grant_number":"Y 564-B12","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425"}],"date_published":"2017-05-02T00:00:00Z","ec_funded":1,"year":"2017","publist_id":"7052","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","abstract":[{"text":"Trafficking cells frequently transmigrate through epithelial and endothelial monolayers. How monolayers cooperate with the penetrating cells to support their transit is poorly understood. We studied dendritic cell (DC) entry into lymphatic capillaries as a model system for transendothelial migration. We find that the chemokine CCL21, which is the decisive guidance cue for intravasation, mainly localizes in the trans-Golgi network and intracellular vesicles of lymphatic endothelial cells. Upon DC transmigration, these Golgi deposits disperse and CCL21 becomes extracellularly enriched at the sites of endothelial cell-cell junctions. When we reconstitute the transmigration process in vitro, we find that secretion of CCL21-positive vesicles is triggered by a DC contact-induced calcium signal, and selective calcium chelation in lymphatic endothelium attenuates transmigration. Altogether, our data demonstrate a chemokine-mediated feedback between DCs and lymphatic endothelium, which facilitates transendothelial migration.","lang":"eng"}],"tmp":{"image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)"},"intvolume":"        19","has_accepted_license":"1","file_date_updated":"2020-07-14T12:47:38Z","publication_status":"published","publication_identifier":{"issn":["22111247"]},"oa_version":"Published Version","title":"Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia","scopus_import":1,"day":"02","author":[{"full_name":"Vaahtomeri, Kari","id":"368EE576-F248-11E8-B48F-1D18A9856A87","last_name":"Vaahtomeri","first_name":"Kari","orcid":"0000-0001-7829-3518"},{"first_name":"Markus","last_name":"Brown","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","full_name":"Brown, Markus"},{"last_name":"Hauschild","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","full_name":"Hauschild, Robert","orcid":"0000-0001-9843-3522","first_name":"Robert"},{"full_name":"De Vries, Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","last_name":"De Vries","first_name":"Ingrid"},{"full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","last_name":"Leithner","first_name":"Alexander F"},{"full_name":"Mehling, Matthias","id":"3C23B994-F248-11E8-B48F-1D18A9856A87","last_name":"Mehling","orcid":"0000-0001-8599-1226","first_name":"Matthias"},{"last_name":"Kaufmann","full_name":"Kaufmann, Walter","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","first_name":"Walter","orcid":"0000-0001-9735-5315"},{"first_name":"Michael K","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt"}],"date_created":"2018-12-11T11:47:50Z","volume":19,"language":[{"iso":"eng"}],"pubrep_id":"900","oa":1,"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"chicago":"Vaahtomeri, Kari, Markus Brown, Robert Hauschild, Ingrid de Vries, Alexander F Leithner, Matthias Mehling, Walter Kaufmann, and Michael K Sixt. “Locally Triggered Release of the Chemokine CCL21 Promotes Dendritic Cell Transmigration across Lymphatic Endothelia.” <i>Cell Reports</i>. Cell Press, 2017. <a href=\"https://doi.org/10.1016/j.celrep.2017.04.027\">https://doi.org/10.1016/j.celrep.2017.04.027</a>.","ista":"Vaahtomeri K, Brown M, Hauschild R, de Vries I, Leithner AF, Mehling M, Kaufmann W, Sixt MK. 2017. Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia. Cell Reports. 19(5), 902–909.","apa":"Vaahtomeri, K., Brown, M., Hauschild, R., de Vries, I., Leithner, A. F., Mehling, M., … Sixt, M. K. (2017). Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia. <i>Cell Reports</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.celrep.2017.04.027\">https://doi.org/10.1016/j.celrep.2017.04.027</a>","mla":"Vaahtomeri, Kari, et al. “Locally Triggered Release of the Chemokine CCL21 Promotes Dendritic Cell Transmigration across Lymphatic Endothelia.” <i>Cell Reports</i>, vol. 19, no. 5, Cell Press, 2017, pp. 902–09, doi:<a href=\"https://doi.org/10.1016/j.celrep.2017.04.027\">10.1016/j.celrep.2017.04.027</a>.","ama":"Vaahtomeri K, Brown M, Hauschild R, et al. Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia. <i>Cell Reports</i>. 2017;19(5):902-909. doi:<a href=\"https://doi.org/10.1016/j.celrep.2017.04.027\">10.1016/j.celrep.2017.04.027</a>","ieee":"K. Vaahtomeri <i>et al.</i>, “Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia,” <i>Cell Reports</i>, vol. 19, no. 5. Cell Press, pp. 902–909, 2017.","short":"K. Vaahtomeri, M. Brown, R. Hauschild, I. de Vries, A.F. Leithner, M. Mehling, W. Kaufmann, M.K. Sixt, Cell Reports 19 (2017) 902–909."},"issue":"5","month":"05","file":[{"creator":"system","date_updated":"2020-07-14T12:47:38Z","date_created":"2018-12-12T10:14:54Z","file_size":2248814,"file_id":"5109","content_type":"application/pdf","access_level":"open_access","file_name":"IST-2017-900-v1+1_1-s2.0-S2211124717305211-main.pdf","checksum":"8fdddaab1f1d76a6ec9ca94dcb6b07a2","relation":"main_file"}],"department":[{"_id":"MiSi"},{"_id":"Bio"},{"_id":"EM-Fac"}]},{"file_date_updated":"2018-12-12T10:09:32Z","publication_status":"published","intvolume":"         6","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"abstract":[{"text":"Cellular locomotion is a central hallmark of eukaryotic life. It is governed by cell-extrinsic molecular factors, which can either emerge in the soluble phase or as immobilized, often adhesive ligands. To encode for direction, every cue must be present as a spatial or temporal gradient. Here, we developed a microfluidic chamber that allows measurement of cell migration in combined response to surface immobilized and soluble molecular gradients. As a proof of principle we study the response of dendritic cells to their major guidance cues, chemokines. The majority of data on chemokine gradient sensing is based on in vitro studies employing soluble gradients. Despite evidence suggesting that in vivo chemokines are often immobilized to sugar residues, limited information is available how cells respond to immobilized chemokines. We tracked migration of dendritic cells towards immobilized gradients of the chemokine CCL21 and varying superimposed soluble gradients of CCL19. Differential migratory patterns illustrate the potential of our setup to quantitatively study the competitive response to both types of gradients. Beyond chemokines our approach is broadly applicable to alternative systems of chemo- and haptotaxis such as cells migrating along gradients of adhesion receptor ligands vs. any soluble cue. \r\n","lang":"eng"}],"has_accepted_license":"1","date_created":"2018-12-11T11:50:27Z","volume":6,"oa_version":"Published Version","title":"A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients","scopus_import":1,"day":"07","author":[{"first_name":"Jan","last_name":"Schwarz","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","full_name":"Schwarz, Jan"},{"id":"3FD04378-F248-11E8-B48F-1D18A9856A87","full_name":"Bierbaum, Veronika","last_name":"Bierbaum","first_name":"Veronika"},{"orcid":"0000-0001-5145-4609","first_name":"Jack","last_name":"Merrin","full_name":"Merrin, Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Tino","full_name":"Frank, Tino","last_name":"Frank"},{"last_name":"Hauschild","full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522","first_name":"Robert"},{"last_name":"Bollenbach","full_name":"Bollenbach, Mark Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","first_name":"Mark Tobias","orcid":"0000-0003-4398-476X"},{"first_name":"Savaş","full_name":"Tay, Savaş","last_name":"Tay"},{"first_name":"Michael K","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt"},{"orcid":"0000-0001-8599-1226","first_name":"Matthias","last_name":"Mehling","full_name":"Mehling, Matthias","id":"3C23B994-F248-11E8-B48F-1D18A9856A87"}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"ieee":"J. Schwarz <i>et al.</i>, “A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients,” <i>Scientific Reports</i>, vol. 6. Nature Publishing Group, 2016.","short":"J. Schwarz, V. Bierbaum, J. Merrin, T. Frank, R. Hauschild, M.T. Bollenbach, S. Tay, M.K. Sixt, M. Mehling, Scientific Reports 6 (2016).","ama":"Schwarz J, Bierbaum V, Merrin J, et al. A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients. <i>Scientific Reports</i>. 2016;6. doi:<a href=\"https://doi.org/10.1038/srep36440\">10.1038/srep36440</a>","apa":"Schwarz, J., Bierbaum, V., Merrin, J., Frank, T., Hauschild, R., Bollenbach, M. T., … Mehling, M. (2016). A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients. <i>Scientific Reports</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/srep36440\">https://doi.org/10.1038/srep36440</a>","mla":"Schwarz, Jan, et al. “A Microfluidic Device for Measuring Cell Migration towards Substrate Bound and Soluble Chemokine Gradients.” <i>Scientific Reports</i>, vol. 6, 36440, Nature Publishing Group, 2016, doi:<a href=\"https://doi.org/10.1038/srep36440\">10.1038/srep36440</a>.","ista":"Schwarz J, Bierbaum V, Merrin J, Frank T, Hauschild R, Bollenbach MT, Tay S, Sixt MK, Mehling M. 2016. A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients. Scientific Reports. 6, 36440.","chicago":"Schwarz, Jan, Veronika Bierbaum, Jack Merrin, Tino Frank, Robert Hauschild, Mark Tobias Bollenbach, Savaş Tay, Michael K Sixt, and Matthias Mehling. “A Microfluidic Device for Measuring Cell Migration towards Substrate Bound and Soluble Chemokine Gradients.” <i>Scientific Reports</i>. Nature Publishing Group, 2016. <a href=\"https://doi.org/10.1038/srep36440\">https://doi.org/10.1038/srep36440</a>."},"language":[{"iso":"eng"}],"pubrep_id":"744","oa":1,"article_number":"36440","file":[{"relation":"main_file","content_type":"application/pdf","access_level":"open_access","file_name":"IST-2017-744-v1+1_srep36440.pdf","file_id":"4756","creator":"system","date_updated":"2018-12-12T10:09:32Z","date_created":"2018-12-12T10:09:32Z","file_size":2353456}],"department":[{"_id":"MiSi"},{"_id":"NanoFab"},{"_id":"Bio"},{"_id":"ToBo"}],"month":"11","quality_controlled":"1","ddc":["579"],"type":"journal_article","_id":"1154","date_updated":"2021-01-12T06:48:41Z","publisher":"Nature Publishing Group","doi":"10.1038/srep36440","date_published":"2016-11-07T00:00:00Z","acknowledgement":"This work was supported by the Swiss National Science Foundation (Ambizione fellowship; PZ00P3-154733 to M.M.), the Swiss Multiple Sclerosis Society (research support to M.M.), a fellowship from the Boehringer Ingelheim Fonds (BIF) to J.S., the European Research Council (grant ERC GA 281556) and a START award from the Austrian Science Foundation (FWF) to M.S. #BioimagingFacility","ec_funded":1,"publication":"Scientific Reports","status":"public","project":[{"grant_number":"281556","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)","call_identifier":"FP7","_id":"25A603A2-B435-11E9-9278-68D0E5697425"},{"_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Y 564-B12","name":"Cytoskeletal force generation and transduction of leukocytes (FWF)"}],"publist_id":"6204","year":"2016"}]