المؤلفون: Theurl I., Hilgendorf I., Nairz M., Tymoszuk P., Haschka D., Asshoff M., He S., Gerhardt L. M. S., Holderried T. A. W., Seifert M., Sopper S., Fenn A. M., Anzai A., Rattik S., McAlpine C., Theurl M., Wieghofer P., Iwamoto Y., Weber G. F., Harder N. K., Chousterman B. G., Arvedson T. L., McKee M., Wang F., Lutz O. M. D., Rezoagli E., Babitt J. L., Berra L., Prinz M., Nahrendorf M., Weiss G., Weissleder R., Lin H. Y., Swirski F. K.

المساهمون: Theurl, I, Hilgendorf, I, Nairz, M, Tymoszuk, P, Haschka, D, Asshoff, M, He, S, Gerhardt, L, Holderried, T, Seifert, M, Sopper, S, Fenn, A, Anzai, A, Rattik, S, Mcalpine, C, Theurl, M, Wieghofer, P, Iwamoto, Y, Weber, G, Harder, N, Chousterman, B, Arvedson, T, Mckee, M, Wang, F, Lutz, O, Rezoagli, E, Babitt, J, Berra, L, Prinz, M, Nahrendorf, M, Weiss, G, Weissleder, R, Lin, H, Swirski, F

مصطلحات موضوعية: Anemia, Hemolytic, Sickle Cell, Animal, Antigens, Ly, Cation Transport Protein, Cell Differentiation, Disease Models, Erythrocyte, Granulocyte-Macrophage Colony-Stimulating Factor, Hepatocyte, Inflammation, Iron, Kupffer Cell, Liver, Macrophage Colony-Stimulating Factor, Macrophage, Membrane Protein, Mice, Monocyte, NF-E2-Related Factor 2, Spleen, MED/41 - ANESTESIOLOGIA

الوصف: Iron is an essential component of the erythrocyte protein hemoglobin and is crucial to oxygen transport in vertebrates. In the steady state, erythrocyte production is in equilibrium with erythrocyte removal. In various pathophysiological conditions, however, erythrocyte life span is compromised severely, which threatens the organism with anemia and iron toxicity. Here we identify an on-demand mechanism that clears erythrocytes and recycles iron. We show that monocytes that express high levels of lymphocyte antigen 6 complex, locus C1 (LY6C1, also known as Ly-6C) ingest stressed and senescent erythrocytes, accumulate in the liver via coordinated chemotactic cues, and differentiate into ferroportin 1 (FPN1, encoded by SLC40A1)-expressing macrophages that can deliver iron to hepatocytes. Monocyte-derived FPN1+Tim-4neg macrophages are transient, reside alongside embryonically derived T cell immunoglobulin and mucin domain containing 4 (Timd4, also known as Tim-4)high Kupffer cells (KCs), and depend on the growth factor Csf1 and the transcription factor Nrf2 (encoded by Nfe2l2). The spleen, likewise, recruits iron-loaded Ly-6Chigh monocytes, but these do not differentiate into iron-recycling macrophages, owing to the suppressive action of Csf2. The accumulation of a transient macrophage population in the liver also occurs in mouse models of hemolytic anemia, anemia of inflammation, and sickle cell disease. Inhibition of monocyte recruitment to the liver during stressed erythrocyte delivery leads to kidney and liver damage. These observations identify the liver as the primary organ that supports rapid erythrocyte removal and iron recycling, and uncover a mechanism by which the body adapts to fluctuations in erythrocyte integrity.

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/27428900; info:eu-repo/semantics/altIdentifier/wos/WOS:000381000200021; volume:22; issue:8; firstpage:945; lastpage:951; numberofpages:7; journal:NATURE MEDICINE; http://hdl.handle.net/10281/287234Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84978733946

الإتاحة: https://doi.org/10.1038/nm.4146Test
http://hdl.handle.net/10281/287234Test

المؤلفون: Nahrendorf, M., Frantz, S., Swirski, F.K., Mulder, W.J., Randolph, G.J., Ertl, G., Ntziachristos, V., Piek, J.J., Stroes, E.S., Schwaiger, M., Mann, D.L., Fayad, Z.A.

المصدر: J. Am. Coll. Cardiol. 65, 1583-1591 (2015)

مصطلحات موضوعية: Atherosclerosis, Heart Failure, Hematopoiesis, Leukocytes, Myocardial Infarction, Spleen

الوصف: While acute myocardial infarction mortality declines, patients continue to face reinfarction and/or heart failure. The immune system, which intimately interacts with healthy and diseased tissues through resident and recruited leukocytes, is a central interface for a global host response to ischemia. Pathways that enhance the systemic leukocyte supply may be potential therapeutic targets. Pre-clinically, imaging helps to identify immunity's decision nodes, which may serve as such targets. In translating the rapidly-expanding pre-clinical data on immune activity, the difficulty of obtaining multiple clinical tissue samples from involved organs is an obstacle that whole-body imaging can help overcome. In patients, molecular and cellular imaging can be integrated with blood-based diagnostics to assess the translatability of discoveries, including the activation of hematopoietic tissues after myocardial infarction, and serve as an endpoint in clinical trials. In this review, we discuss these concepts while focusing on imaging immune activity in organs involved in ischemic heart disease.

وصف الملف: application/pdf

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/25881940; info:eu-repo/semantics/altIdentifier/wos/WOS:000352956500012; info:eu-repo/semantics/altIdentifier/isbn/0735-1097; info:eu-repo/semantics; https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=44433Test; urn:isbn:0735-1097; urn:issn:0735-1097; urn:issn:1558-3597

الإتاحة: https://doi.org/10.1016/j.jacc.2015.02.034Test
https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=44433Test

المؤلفون: Piotr Tymoszuk, Atsushi Anzai, Cameron S. McAlpine, David Haschka, Manfred Nairz, Herbert Y. Lin, Shun He, Peter Wieghofer, Ingo Hilgendorf, Filip K. Swirski, Fudi Wang, Marco Prinz, Sara Rattik, Malte Asshoff, Guenter Weiss, Jodie L. Babitt, Louisa M.S. Gerhardt, Milan Theurl, Mary McKee, Matthias Nahrendorf, Nina K. Harder, Ashley M. Fenn, Markus Seifert, Lorenzo Berra, Tobias A. W. Holderried, Georg F. Weber, Yoshiko Iwamoto, Benjamin G. Chousterman, Sieghart Sopper, Igor Theurl, Oliver M D Lutz, Ralph Weissleder, Emanuele Rezoagli, Tara Arvedson

المساهمون: Theurl, I, Hilgendorf, I, Nairz, M, Tymoszuk, P, Haschka, D, Asshoff, M, He, S, Gerhardt, L, Holderried, T, Seifert, M, Sopper, S, Fenn, A, Anzai, A, Rattik, S, Mcalpine, C, Theurl, M, Wieghofer, P, Iwamoto, Y, Weber, G, Harder, N, Chousterman, B, Arvedson, T, Mckee, M, Wang, F, Lutz, O, Rezoagli, E, Babitt, J, Berra, L, Prinz, M, Nahrendorf, M, Weiss, G, Weissleder, R, Lin, H, Swirski, F

المصدر: Nature medicine

مصطلحات موضوعية: 0301 basic medicine, Hemolytic anemia, Erythrocytes, Macrophage, Monocyte, Monocytes, Mice, Antigens, Ly, Hepatocyte, Cation Transport Proteins, Membrane Protein, Anemia, Cell Differentiation, General Medicine, Cell biology, Erythrocyte, medicine.anatomical_structure, Biochemistry, Liver, Kupffer Cell, Antibody, medicine.symptom, Anemia, Hemolytic, Kupffer Cells, NF-E2-Related Factor 2, T cell, Iron, Inflammation, Spleen, Anemia, Sickle Cell, Biology, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, medicine, Animals, MED/41 - ANESTESIOLOGIA, Animal, Macrophages, Macrophage Colony-Stimulating Factor, Oxygen transport, Membrane Proteins, Granulocyte-Macrophage Colony-Stimulating Factor, medicine.disease, Disease Models, Animal, 030104 developmental biology, Cation Transport Protein, Hepatocytes, biology.protein, Hemoglobin

الوصف: Iron is an essential component of the erythrocyte protein hemoglobin and is crucial to oxygen transport in vertebrates. In the steady state, erythrocyte production is in equilibrium with erythrocyte removal. In various pathophysiological conditions, however, erythrocyte life span is compromised severely, which threatens the organism with anemia and iron toxicity. Here we identify an on-demand mechanism that clears erythrocytes and recycles iron. We show that monocytes that express high levels of lymphocyte antigen 6 complex, locus C1 (LY6C1, also known as Ly-6C) ingest stressed and senescent erythrocytes, accumulate in the liver via coordinated chemotactic cues, and differentiate into ferroportin 1 (FPN1, encoded by SLC40A1)-expressing macrophages that can deliver iron to hepatocytes. Monocyte-derived FPN1(+)Tim-4(neg) macrophages are transient, reside alongside embryonically derived T cell immunoglobulin and mucin domain containing 4 (Timd4, also known as Tim-4)(high) Kupffer cells (KCs), and depend on the growth factor Csf1 and the transcription factor Nrf2 (encoded by Nfe2l2). The spleen, likewise, recruits iron-loaded Ly-6C(high) monocytes, but these do not differentiate into iron-recycling macrophages, owing to the suppressive action of Csf2. The accumulation of a transient macrophage population in the liver also occurs in mouse models of hemolytic anemia, anemia of inflammation, and sickle cell disease. Inhibition of monocyte recruitment to the liver during stressed erythrocyte delivery leads to kidney and liver damage. These observations identify the liver as the primary organ that supports rapid erythrocyte removal and iron recycling, and uncover a mechanism by which the body adapts to fluctuations in erythrocyte integrity.

وصف الملف: ELETTRONICO; application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::891a35af19c657b26ac467c04e166326Test
http://hdl.handle.net/10281/287234Test