Nicolas Tessandier1,2, Imene Melki1,2, Nathalie Cloutier1,2, Isabelle Allaeys1,2, Adam Miszta3,4, Sisareuth Tan5, Andreea Milasan6, Sara Michel1,2, Abderrahim Benmoussa7, Tania Lévesque1,2, Francine Côté8, Steven E McKenzie9, Caroline Gilbert1,2, Patrick Provost1,2, Alain R Brisson5, Alisa S Wolberg3, Paul R Fortin1,2,10, Catherine Martel6,4, Éric Boilard1,2,10. 1. From the Centre de recherche du CHU de Québec, Canada (N.T., I.M., N.C., I.A., S.M., T.L., C.G., P.P., P.R.F., E.B.). 2. Département de microbiologie-infectiologie et d'immunologie, Université Laval, QC, Canada (N.T., I.M., N.C., I.A., S.M., T.L., C.G., P.P., P.R.F., E.B.). 3. Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill (A.M., A.S.W.). 4. Montreal Heart Institute, Quebec, Canada (A.M., C.M.). 5. Extracellular Vesicles and Membrane Repair, UMR-5248-CBMN CNRS-University of Bordeaux-IPB, Allée Geoffroy Saint-Hilaire, Pessac, France (S.T., A.R.B.). 6. Department of Medicine, Faculty of Medicine (A.M., C.M.), Université de Montréal, Quebec, Canada. 7. Department of Nutrition, CHU Sainte-Justine (A.B.), Université de Montréal, Quebec, Canada. 8. Institut Imagine, Inserm U1163, Laboratoire Olivier Hermine, Paris, France (F.C.). 9. Cardeza Foundation for Hematological Research, Thomas Jefferson University, Philadelphia, PA (S.E.M.). 10. Axe maladies infectieuses et inflammatoires, Centre de recherche du CHU de Québec-Université Laval, Québec, Canada (P.R.F., E.B.).
Abstract
OBJECTIVE: The lymphatic system is a circulatory system that unidirectionally drains the interstitial tissue fluid back to blood circulation. Although lymph is utilized by leukocytes for immune surveillance, it remains inaccessible to platelets and erythrocytes. Activated cells release submicron extracellular vesicles (EV) that transport molecules from the donor cell. In rheumatoid arthritis, EV accumulate in the joint where they can interact with numerous cellular lineages. However, whether EV can exit the inflamed tissue to recirculate is unknown. Here, we investigated whether vascular leakage that occurs during inflammation could favor EV access to the lymphatic system. Approach and Results: Using an in vivo model of autoimmune inflammatory arthritis, we show that there is an influx of platelet EV, but not EV from erythrocytes or leukocytes, in joint-draining lymph. In contrast to blood platelet EV, lymph platelet EV lacked mitochondrial organelles and failed to promote coagulation. Platelet EV influx in lymph was consistent with joint vascular leakage and implicated the fibrinogen receptor α2bβ3 and platelet-derived serotonin. CONCLUSIONS: These findings show that platelets can disseminate their EV in fluid that is inaccessible to platelets and beyond the joint in this disease.
OBJECTIVE: The lymphatic system is a circulatory system that unidirectionally drains the interstitial tissue fluid back to blood circulation. Although lymph is utilized by leukocytes for immune surveillance, it remains inaccessible to platelets and erythrocytes. Activated cells release submicron extracellular vesicles (EV) that transport molecules from the donor cell. In rheumatoid arthritis, EV accumulate in the joint where they can interact with numerous cellular lineages. However, whether EV can exit the inflamed tissue to recirculate is unknown. Here, we investigated whether vascular leakage that occurs during inflammation could favor EV access to the lymphatic system. Approach and Results: Using an in vivo model of autoimmune inflammatory arthritis, we show that there is an influx of platelet EV, but not EV from erythrocytes or leukocytes, in joint-draining lymph. In contrast to blood platelet EV, lymph platelet EV lacked mitochondrial organelles and failed to promote coagulation. Platelet EV influx in lymph was consistent with joint vascular leakage and implicated the fibrinogen receptor α2bβ3 and platelet-derived serotonin. CONCLUSIONS: These findings show that platelets can disseminate their EV in fluid that is inaccessible to platelets and beyond the joint in this disease.
Authors: Vinatha Sreeramkumar; José M Adrover; Ivan Ballesteros; Maria Isabel Cuartero; Jan Rossaint; Izaskun Bilbao; Maria Nácher; Christophe Pitaval; Irena Radovanovic; Yoshinori Fukui; Rodger P McEver; Marie-Dominique Filippi; Ignacio Lizasoain; Jesús Ruiz-Cabello; Alexander Zarbock; María A Moro; Andrés Hidalgo Journal: Science Date: 2014-12-04 Impact factor: 47.728
Authors: Nathalie Cloutier; Sisareuth Tan; Luc H Boudreau; Catriona Cramb; Roopashree Subbaiah; Lauren Lahey; Alexandra Albert; Ruslan Shnayder; Reuben Gobezie; Peter A Nigrovic; Richard W Farndale; William H Robinson; Alain Brisson; David M Lee; Eric Boilard Journal: EMBO Mol Med Date: 2012-12-11 Impact factor: 12.137
Authors: Bence György; Tamás G Szabó; Lilla Turiák; Matthew Wright; Petra Herczeg; Zsigmond Lédeczi; Agnes Kittel; Anna Polgár; Kálmán Tóth; Beáta Dérfalvi; Gergő Zelenák; István Böröcz; Bob Carr; György Nagy; Károly Vékey; Steffen Gay; András Falus; Edit I Buzás Journal: PLoS One Date: 2012-11-20 Impact factor: 3.240
Authors: Qiaoli Ma; Lothar C Dieterich; Kristian Ikenberg; Samia B Bachmann; Johanna Mangana; Steven T Proulx; Valerie C Amann; Mitchell P Levesque; Reinhard Dummer; Peter Baluk; Donald M McDonald; Michael Detmar Journal: Sci Adv Date: 2018-08-08 Impact factor: 14.136
Authors: Hara T Georgatzakou; Sotirios P Fortis; Effie G Papageorgiou; Marianna H Antonelou; Anastasios G Kriebardis Journal: Biomolecules Date: 2022-06-08
Authors: Abi G Yates; Ryan C Pink; Uta Erdbrügger; Pia R-M Siljander; Elizabeth R Dellar; Paschalia Pantazi; Naveed Akbar; William R Cooke; Manu Vatish; Emmanuel Dias-Neto; Daniel C Anthony; Yvonne Couch Journal: J Extracell Vesicles Date: 2022-01