Impaired lymphatic contraction associated with immunosuppression
Identifieur interne : 004E25 ( Main/Exploration ); précédent : 004E24; suivant : 004E26Impaired lymphatic contraction associated with immunosuppression
Auteurs : Shan Liao [États-Unis] ; Gang Cheng [États-Unis] ; David A. Conner [États-Unis] ; Yuhui Huang [États-Unis] ; Raju S. Kucherlapati [États-Unis] ; Lance L. Munn [États-Unis] ; Nancy H. Ruddle [États-Unis] ; Rakesh K. Jain [États-Unis] ; Dai Fukumura [États-Unis] ; Timothy P. Padera [États-Unis]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2011.
Descripteurs français
- KwdFr :
- 4-Éthoxyméthylène-2-phényl-oxazol-5(4H)-one (pharmacologie), Animaux, Antigènes CD11b (biosynthèse), Cellules de la moelle osseuse (cytologie), Cinétique, Immunosuppression thérapeutique, Inflammation, Microscopie (), Métastase lymphatique, Nitric oxide synthase type III (métabolisme), Peau (), Souris, Souris de lignée C57BL, Système immunitaire, Système lymphatique (physiologie), Vaisseaux lymphatiques (), Vaisseaux lymphatiques (anatomopathologie).
- MESH :
- anatomopathologie : Vaisseaux lymphatiques.
- biosynthèse : Antigènes CD11b.
- cytologie : Cellules de la moelle osseuse.
- métabolisme : Nitric oxide synthase type III.
- pharmacologie : 4-Éthoxyméthylène-2-phényl-oxazol-5(4H)-one.
- physiologie : Système lymphatique.
- Animaux, Cinétique, Immunosuppression thérapeutique, Inflammation, Microscopie, Métastase lymphatique, Peau, Souris, Souris de lignée C57BL, Système immunitaire, Vaisseaux lymphatiques.
English descriptors
- KwdEn :
- Animals, Antigens, CD11b (biosynthesis), Bone Marrow Cells (cytology), Immune System, Immunosuppression, Inflammation, Kinetics, Lymphatic Metastasis, Lymphatic System (physiology), Lymphatic Vessels (drug effects), Lymphatic Vessels (pathology), Mice, Mice, Inbred C57BL, Microscopy (methods), Nitric Oxide Synthase Type III (metabolism), Oxazolone (pharmacology), Skin (drug effects).
- MESH :
- chemical , biosynthesis : Antigens, CD11b.
- cytology : Bone Marrow Cells.
- drug effects : Lymphatic Vessels, Skin.
- chemical , metabolism : Nitric Oxide Synthase Type III.
- methods : Microscopy.
- pathology : Lymphatic Vessels.
- chemical , pharmacology : Oxazolone.
- physiology : Lymphatic System.
- Animals, Immune System, Immunosuppression, Inflammation, Kinetics, Lymphatic Metastasis, Mice, Mice, Inbred C57BL.
Abstract
To trigger an effective immune response, antigen and antigen-presenting cells travel to the lymph nodes via collecting lymphatic vessels. However, our understanding of the regulation of collecting lymphatic vessel function and lymph transport is limited. To dissect the molecular control of lymphatic function, we developed a unique mouse model that allows intravital imaging of autonomous lymphatic vessel contraction. Using this method, we demonstrated that endothelial nitric oxide synthase (eNOS) in lymphatic endothelial cells is required for robust lymphatic contractions under physiological conditions. By contrast, under inflammatory conditions, inducible NOS (iNOS)-expressing CD11b+Gr-1+ cells attenuate lymphatic contraction. This inhibition of lymphatic contraction was associated with a reduction in the response to antigen in a model of immune-induced multiple sclerosis. These results suggest the suppression of lymphatic function by the CD11b+Gr-1+ cells as a potential mechanism of self-protection from autoreactive responses during on-going inflammation. The central role for nitric oxide also suggests that other diseases such as cancer and infection may also mediate lymphatic contraction and thus immune response. Our unique method allows the study of lymphatic function and its molecular regulation during inflammation, lymphedema, and lymphatic metastasis.
Url:
DOI: 10.1073/pnas.1116152108
PubMed: 22065738
PubMed Central: 3219138
Affiliations:
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Le document en format XML
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Steele Laboratory, Department of Radiation Oncology, Harvard Medical School<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>, Boston</wicri:cityArea></affiliation></author><author><name sortKey="Kucherlapati, Raju S" sort="Kucherlapati, Raju S" uniqKey="Kucherlapati R" first="Raju S." last="Kucherlapati">Raju S. Kucherlapati</name><affiliation wicri:level="2"><nlm:aff wicri:cut="; and" id="aff2">Department of Genetics,<institution>Brigham and Women's Hospital</institution>, Boston, MA 02115</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>, Boston</wicri:cityArea></affiliation></author><author><name sortKey="Munn, Lance L" sort="Munn, Lance L" uniqKey="Munn L" first="Lance L." last="Munn">Lance L. Munn</name><affiliation wicri:level="2"><nlm:aff wicri:cut=" and" id="aff1">E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>, Boston</wicri:cityArea></affiliation></author><author><name sortKey="Ruddle, Nancy H" sort="Ruddle, Nancy H" uniqKey="Ruddle N" first="Nancy H." last="Ruddle">Nancy H. 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L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>, Boston</wicri:cityArea></affiliation></author><author><name sortKey="Cheng, Gang" sort="Cheng, Gang" uniqKey="Cheng G" first="Gang" last="Cheng">Gang Cheng</name><affiliation wicri:level="2"><nlm:aff wicri:cut=" and" id="aff1">E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>, Boston</wicri:cityArea></affiliation></author><author><name sortKey="Conner, David A" sort="Conner, David A" uniqKey="Conner D" first="David A." last="Conner">David A. Conner</name><affiliation wicri:level="2"><nlm:aff wicri:cut="; and" id="aff2">Department of Genetics,<institution>Brigham and Women's Hospital</institution>, Boston, MA 02115</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>, Boston</wicri:cityArea></affiliation></author><author><name sortKey="Huang, Yuhui" sort="Huang, Yuhui" uniqKey="Huang Y" first="Yuhui" last="Huang">Yuhui Huang</name><affiliation wicri:level="2"><nlm:aff wicri:cut=" and" id="aff1">E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>, Boston</wicri:cityArea></affiliation></author><author><name sortKey="Kucherlapati, Raju S" sort="Kucherlapati, Raju S" uniqKey="Kucherlapati R" first="Raju S." last="Kucherlapati">Raju S. Kucherlapati</name><affiliation wicri:level="2"><nlm:aff wicri:cut="; and" id="aff2">Department of Genetics,<institution>Brigham and Women's Hospital</institution>, Boston, MA 02115</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>, Boston</wicri:cityArea></affiliation></author><author><name sortKey="Munn, Lance L" sort="Munn, Lance L" uniqKey="Munn L" first="Lance L." last="Munn">Lance L. Munn</name><affiliation wicri:level="2"><nlm:aff wicri:cut=" and" id="aff1">E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>, Boston</wicri:cityArea></affiliation></author><author><name sortKey="Ruddle, Nancy H" sort="Ruddle, Nancy H" uniqKey="Ruddle N" first="Nancy H." last="Ruddle">Nancy H. Ruddle</name><affiliation wicri:level="2"><nlm:aff id="aff3">Departments of Epidemiology and Public Health and Immunobiology,<institution>Yale University School of Medicine</institution>, New Haven, CT 06511</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>, New Haven</wicri:cityArea></affiliation></author><author><name sortKey="Jain, Rakesh K" sort="Jain, Rakesh K" uniqKey="Jain R" first="Rakesh K." last="Jain">Rakesh K. Jain</name><affiliation wicri:level="2"><nlm:aff wicri:cut=" and" id="aff1">E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>, Boston</wicri:cityArea></affiliation></author><author><name sortKey="Fukumura, Dai" sort="Fukumura, Dai" uniqKey="Fukumura D" first="Dai" last="Fukumura">Dai Fukumura</name><affiliation wicri:level="2"><nlm:aff wicri:cut=" and" id="aff1">E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>, Boston</wicri:cityArea></affiliation></author><author><name sortKey="Padera, Timothy P" sort="Padera, Timothy P" uniqKey="Padera T" first="Timothy P." last="Padera">Timothy P. Padera</name><affiliation wicri:level="2"><nlm:aff wicri:cut=" and" id="aff1">E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>, Boston</wicri:cityArea></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antigens, CD11b (biosynthesis)</term><term>Bone Marrow Cells (cytology)</term><term>Immune System</term><term>Immunosuppression</term><term>Inflammation</term><term>Kinetics</term><term>Lymphatic Metastasis</term><term>Lymphatic System (physiology)</term><term>Lymphatic Vessels (drug effects)</term><term>Lymphatic Vessels (pathology)</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Microscopy (methods)</term><term>Nitric Oxide Synthase Type III (metabolism)</term><term>Oxazolone (pharmacology)</term><term>Skin (drug effects)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>4-Éthoxyméthylène-2-phényl-oxazol-5(4H)-one (pharmacologie)</term><term>Animaux</term><term>Antigènes CD11b (biosynthèse)</term><term>Cellules de la moelle osseuse (cytologie)</term><term>Cinétique</term><term>Immunosuppression thérapeutique</term><term>Inflammation</term><term>Microscopie ()</term><term>Métastase lymphatique</term><term>Nitric oxide synthase type III (métabolisme)</term><term>Peau ()</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Système immunitaire</term><term>Système lymphatique (physiologie)</term><term>Vaisseaux lymphatiques ()</term><term>Vaisseaux lymphatiques (anatomopathologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Antigens, CD11b</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Vaisseaux lymphatiques</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Antigènes CD11b</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Cellules de la moelle osseuse</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Bone Marrow Cells</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Lymphatic Vessels</term><term>Skin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Nitric Oxide Synthase Type III</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Microscopy</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Nitric oxide synthase type III</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lymphatic Vessels</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>4-Éthoxyméthylène-2-phényl-oxazol-5(4H)-one</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Oxazolone</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Système lymphatique</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Lymphatic System</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Immune System</term><term>Immunosuppression</term><term>Inflammation</term><term>Kinetics</term><term>Lymphatic Metastasis</term><term>Mice</term><term>Mice, Inbred C57BL</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cinétique</term><term>Immunosuppression thérapeutique</term><term>Inflammation</term><term>Microscopie</term><term>Métastase lymphatique</term><term>Peau</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Système immunitaire</term><term>Vaisseaux lymphatiques</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>To trigger an effective immune response, antigen and antigen-presenting cells travel to the lymph nodes via collecting lymphatic vessels. However, our understanding of the regulation of collecting lymphatic vessel function and lymph transport is limited. To dissect the molecular control of lymphatic function, we developed a unique mouse model that allows intravital imaging of autonomous lymphatic vessel contraction. Using this method, we demonstrated that endothelial nitric oxide synthase (eNOS) in lymphatic endothelial cells is required for robust lymphatic contractions under physiological conditions. By contrast, under inflammatory conditions, inducible NOS (iNOS)-expressing CD11b<sup>+</sup>Gr-1<sup>+</sup> cells attenuate lymphatic contraction. This inhibition of lymphatic contraction was associated with a reduction in the response to antigen in a model of immune-induced multiple sclerosis. These results suggest the suppression of lymphatic function by the CD11b<sup>+</sup>Gr-1<sup>+</sup> cells as a potential mechanism of self-protection from autoreactive responses during on-going inflammation. The central role for nitric oxide also suggests that other diseases such as cancer and infection may also mediate lymphatic contraction and thus immune response. Our unique method allows the study of lymphatic function and its molecular regulation during inflammation, lymphedema, and lymphatic metastasis.</p></div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Connecticut</li><li>Massachusetts</li></region></list><tree><country name="États-Unis"><region name="Massachusetts"><name sortKey="Liao, Shan" sort="Liao, Shan" uniqKey="Liao S" first="Shan" last="Liao">Shan Liao</name></region><name sortKey="Cheng, Gang" sort="Cheng, Gang" uniqKey="Cheng G" first="Gang" last="Cheng">Gang Cheng</name><name sortKey="Conner, David A" sort="Conner, David A" uniqKey="Conner D" first="David A." last="Conner">David A. Conner</name><name sortKey="Fukumura, Dai" sort="Fukumura, Dai" uniqKey="Fukumura D" first="Dai" last="Fukumura">Dai Fukumura</name><name sortKey="Huang, Yuhui" sort="Huang, Yuhui" uniqKey="Huang Y" first="Yuhui" last="Huang">Yuhui Huang</name><name sortKey="Jain, Rakesh K" sort="Jain, Rakesh K" uniqKey="Jain R" first="Rakesh K." last="Jain">Rakesh K. Jain</name><name sortKey="Kucherlapati, Raju S" sort="Kucherlapati, Raju S" uniqKey="Kucherlapati R" first="Raju S." last="Kucherlapati">Raju S. Kucherlapati</name><name sortKey="Munn, Lance L" sort="Munn, Lance L" uniqKey="Munn L" first="Lance L." last="Munn">Lance L. Munn</name><name sortKey="Padera, Timothy P" sort="Padera, Timothy P" uniqKey="Padera T" first="Timothy P." last="Padera">Timothy P. Padera</name><name sortKey="Ruddle, Nancy H" sort="Ruddle, Nancy H" uniqKey="Ruddle N" first="Nancy H." last="Ruddle">Nancy H. Ruddle</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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