Profound but Dysfunctional Lymphangiogenesis via Vascular Endothelial Growth Factor Ligands from CD11b+ Macrophages in Advanced Ovarian Cancer

Jeon, Bong-Hyun; Jang, Cholsoon; Han, Joungho; Kataru, Raghu P.; Piao, Lianhua; Jung, Keehoon; Ji, Hye Young; Schwendener, Reto A.; Jang, Kyu Yun; Kim, Kwan-Sik; Alitalo, Kari; Koh, Gou Young

doi:10.1158/0008-5472.can-07-2572

Cited by 111 publications

(95 citation statements)

References 48 publications

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“…Although lymphangiogenesis and vessel dilation are thought to increase the delivery of lymph to the draining lymph node, a decrease in drainage has also been observed during inflammation and surrounding some cancers (1,2,7). Whether reductions in collecting lymphatic function can affect subsequent immune response by limiting entry of antigen/dendritic cells (DCs) into the draining lymph node (LN) is not known.…”

mentioning

confidence: 99%

Impaired lymphatic contraction associated with immunosuppression

Liao

Cheng

Conner

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

262

321

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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.

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mentioning

confidence: 99%

Impaired lymphatic contraction associated with immunosuppression

Liao

Cheng

Conner

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

262

321

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“…In addition to the tissue fluid homeostasis, the lymphatic system serves as a conduit for trafficking of lymphocytes and antigenpresenting cells to regional lymph nodes, where the immune system encounters pathogens, microbes, and other immune elicitors. Lymphnode lymphatic vessels, which uptake various antigens from peripheral tissues, are positively regulated by chemokines/cytokines secreted by B cells, macrophages, and dendritic cells during inflammation (Jeon et al 2008;Kataru et al 2009;Kim et al 2009). Toll-like receptor (TLR)-4 is highly expressed in LECs and contributes to lipopolysaccharide (LPS)-induced lymphangiogenesis by chemotactic recruitment of macrophages ).…”

mentioning

confidence: 99%

The New Era of the Lymphatic System: No Longer Secondary to the Blood Vascular System

Choi

Lee²,

Hong

2012

Cold Spring Harbor Perspectives in Medicine

118

107

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The blood and lymphatic systems are the two major circulatory systems in our body. Although the blood system has been studied extensively, the lymphatic system has received much less scientific and medical attention because of its elusive morphology and mysterious pathophysiology. However, a series of landmark discoveries made in the past decade has begun to change the previous misconception of the lymphatic system to be secondary to the more essential blood vascular system. In this article, we review the current understanding of the development and pathology of the lymphatic system. We hope to convince readers that the lymphatic system is no less essential than the blood circulatory system for human health and well-being.

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“…Inhibition of COX-2 in macrophages and tumor cells results in a reduction of VEGF-C expression mainly by macrophages. In a closely related model, intraperitoneal injection of human ovarian cancer cell lines in mice induced carcinomatosis and lymphangiogenesis in diaphragm and mesentery (Jeon et al 2008). However, similar to the situation in LPS-induced peritoneal lymphangiogenesis, this lymphangiogenesis is dysfunctional as assessed by tracer injection into the peritoneum ).…”

Section: Leukocytes Tumor Lymphangiogenesis and Lymph Node Metastasismentioning

confidence: 89%

Myeloid Cells and Lymphangiogenesis

Zumsteg

2012

Cold Spring Harbor Perspectives in Medicine

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The lymphatic vascular system and the hematopoietic system are intimately connected in ontogeny and in physiology. During embryonic development, mammalian species derive a first lymphatic vascular plexus from the previously formed anterior cardinal vein, whereas birds and amphibians have a lymphatic vascular system of dual origin, composed of lymphatic endothelial cells (LECs) of venous origin combined with LECs derived from mesenchymal lymphangioblasts. The contribution of hematopoietic cells as building blocks of nascent lymphatic structures in mammals is still under debate. In contrast, the importance of myeloid cells to direct lymphatic vessel growth and function postnatally has been experimentally shown. For example, myeloid cells communicate with LECs via paracrine factors or cell -cell contacts, and they also can acquire lymphatic endothelial morphology and marker gene expression, a process reminiscent of developmental vasculogenesis. Here, we present an overview of the current understanding of how lymphatic vessels and the hematopoietic system, in particular myeloid cells, interact during embryonic development, in normal organ physiology, and in disease.

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Profound but Dysfunctional Lymphangiogenesis via Vascular Endothelial Growth Factor Ligands from CD11b+ Macrophages in Advanced Ovarian Cancer

Cited by 111 publications

References 48 publications

Impaired lymphatic contraction associated with immunosuppression

Impaired lymphatic contraction associated with immunosuppression

The New Era of the Lymphatic System: No Longer Secondary to the Blood Vascular System

Myeloid Cells and Lymphangiogenesis

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