--- _id: '672' abstract: - lang: eng 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. article_processing_charge: Yes author: - first_name: Kari full_name: Vaahtomeri, Kari id: 368EE576-F248-11E8-B48F-1D18A9856A87 last_name: Vaahtomeri orcid: 0000-0001-7829-3518 - first_name: Markus full_name: Brown, Markus id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87 last_name: Brown - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Ingrid full_name: De Vries, Ingrid id: 4C7D837E-F248-11E8-B48F-1D18A9856A87 last_name: De Vries - first_name: Alexander F full_name: Leithner, Alexander F id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87 last_name: Leithner - first_name: Matthias full_name: Mehling, Matthias id: 3C23B994-F248-11E8-B48F-1D18A9856A87 last_name: Mehling orcid: 0000-0001-8599-1226 - first_name: Walter full_name: Kaufmann, Walter id: 3F99E422-F248-11E8-B48F-1D18A9856A87 last_name: Kaufmann orcid: 0000-0001-9735-5315 - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 citation: ama: Vaahtomeri K, Brown M, Hauschild R, et al. Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia. Cell Reports. 2017;19(5):902-909. doi:10.1016/j.celrep.2017.04.027 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. Cell Reports. Cell Press. https://doi.org/10.1016/j.celrep.2017.04.027 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.” Cell Reports. Cell Press, 2017. https://doi.org/10.1016/j.celrep.2017.04.027. ieee: K. Vaahtomeri et al., “Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia,” Cell Reports, vol. 19, no. 5. Cell Press, pp. 902–909, 2017. 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. mla: Vaahtomeri, Kari, et al. “Locally Triggered Release of the Chemokine CCL21 Promotes Dendritic Cell Transmigration across Lymphatic Endothelia.” Cell Reports, vol. 19, no. 5, Cell Press, 2017, pp. 902–09, doi:10.1016/j.celrep.2017.04.027. 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. date_created: 2018-12-11T11:47:50Z date_published: 2017-05-02T00:00:00Z date_updated: 2023-02-23T12:50:09Z day: '02' ddc: - '570' department: - _id: MiSi - _id: Bio - _id: EM-Fac doi: 10.1016/j.celrep.2017.04.027 ec_funded: 1 file: - access_level: open_access checksum: 8fdddaab1f1d76a6ec9ca94dcb6b07a2 content_type: application/pdf creator: system date_created: 2018-12-12T10:14:54Z date_updated: 2020-07-14T12:47:38Z file_id: '5109' file_name: IST-2017-900-v1+1_1-s2.0-S2211124717305211-main.pdf file_size: 2248814 relation: main_file file_date_updated: 2020-07-14T12:47:38Z has_accepted_license: '1' intvolume: ' 19' issue: '5' language: - iso: eng license: https://creativecommons.org/licenses/by-nc-nd/4.0/ month: '05' oa: 1 oa_version: Published Version page: 902 - 909 project: - _id: 25A603A2-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '281556' name: Cytoskeletal force generation and force transduction of migrating leukocytes (EU) - _id: 25A8E5EA-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Y 564-B12 name: Cytoskeletal force generation and transduction of leukocytes (FWF) publication: Cell Reports publication_identifier: issn: - '22111247' publication_status: published publisher: Cell Press publist_id: '7052' pubrep_id: '900' quality_controlled: '1' scopus_import: 1 status: public title: Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 19 year: '2017' ... --- _id: '1154' abstract: - lang: eng 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" 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' article_number: '36440' author: - first_name: Jan full_name: Schwarz, Jan id: 346C1EC6-F248-11E8-B48F-1D18A9856A87 last_name: Schwarz - first_name: Veronika full_name: Bierbaum, Veronika id: 3FD04378-F248-11E8-B48F-1D18A9856A87 last_name: Bierbaum - first_name: Jack full_name: Merrin, Jack id: 4515C308-F248-11E8-B48F-1D18A9856A87 last_name: Merrin orcid: 0000-0001-5145-4609 - first_name: Tino full_name: Frank, Tino last_name: Frank - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Mark Tobias full_name: Bollenbach, Mark Tobias id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87 last_name: Bollenbach orcid: 0000-0003-4398-476X - first_name: Savaş full_name: Tay, Savaş last_name: Tay - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 - first_name: Matthias full_name: Mehling, Matthias id: 3C23B994-F248-11E8-B48F-1D18A9856A87 last_name: Mehling orcid: 0000-0001-8599-1226 citation: ama: Schwarz J, Bierbaum V, Merrin J, et al. A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients. Scientific Reports. 2016;6. doi:10.1038/srep36440 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. Scientific Reports. Nature Publishing Group. https://doi.org/10.1038/srep36440 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.” Scientific Reports. Nature Publishing Group, 2016. https://doi.org/10.1038/srep36440. ieee: J. Schwarz et al., “A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients,” Scientific Reports, vol. 6. Nature Publishing Group, 2016. 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. mla: Schwarz, Jan, et al. “A Microfluidic Device for Measuring Cell Migration towards Substrate Bound and Soluble Chemokine Gradients.” Scientific Reports, vol. 6, 36440, Nature Publishing Group, 2016, doi:10.1038/srep36440. 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). date_created: 2018-12-11T11:50:27Z date_published: 2016-11-07T00:00:00Z date_updated: 2021-01-12T06:48:41Z day: '07' ddc: - '579' department: - _id: MiSi - _id: NanoFab - _id: Bio - _id: ToBo doi: 10.1038/srep36440 ec_funded: 1 file: - access_level: open_access content_type: application/pdf creator: system date_created: 2018-12-12T10:09:32Z date_updated: 2018-12-12T10:09:32Z file_id: '4756' file_name: IST-2017-744-v1+1_srep36440.pdf file_size: 2353456 relation: main_file file_date_updated: 2018-12-12T10:09:32Z has_accepted_license: '1' intvolume: ' 6' language: - iso: eng month: '11' oa: 1 oa_version: Published Version project: - _id: 25A603A2-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '281556' name: Cytoskeletal force generation and force transduction of migrating leukocytes (EU) - _id: 25A8E5EA-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Y 564-B12 name: Cytoskeletal force generation and transduction of leukocytes (FWF) publication: Scientific Reports publication_status: published publisher: Nature Publishing Group publist_id: '6204' pubrep_id: '744' quality_controlled: '1' scopus_import: 1 status: public title: A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 6 year: '2016' ...