title: Impaired lymphatic contraction associated with immunosuppression.
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.
authors: EL Steele Laboratory, Department of Radiation Oncology, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114, USA.
authors: Shan
authors: S
authors: Liao
authors: Gang
authors: G
authors: Cheng
authors: David A
authors: DA
authors: Conner
authors: Yuhui
authors: Y
authors: Huang
authors: Raju S
authors: RS
authors: Kucherlapati
authors: Lance L
authors: LL
authors: Munn
authors: Nancy H
authors: NH
authors: Ruddle
authors: Rakesh K
authors: RK
authors: Jain
authors: Dai
authors: D
authors: Fukumura
authors: Timothy P
authors: TP
authors: Padera
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D039481:CD11b Antigen / Q000096:biosynthesis; D007107:Immune System; D007165:Immunosuppression Therapy; D007249:Inflammation; D007700:Kinetics; D008207:Lymphatic Metastasis; D008208:Lymphatic System / Q000502:physiology*; D042601:Lymphatic Vessels / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008853:Microscopy / Q000379:methods; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010081:Oxazolone / Q000494:pharmacology; D012867:Skin / Q000187:drug effects
chemical_list: D039481:CD11b Antigen; D010081:Oxazolone; D052250:Nitric Oxide Synthase Type III