Inflammation-induced lymphangiogenesis in the cornea arises from CD11b-positive macrophages

Maruyama, Kouichi; Ii, Masaaki; Cursiefen, Claus; Jackson, David G.; Keino, Hiroshi; Tomita, Minoru; Rooijen, Nico van; Takenaka, Hideya; D'Amore, Patricia A.; Stein‐Streilein, Joan; Losordo, Douglas W.; Streilein, J. Wayne

doi:10.1172/jci23874

Cited by 633 publications

(681 citation statements)

References 36 publications

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“…Interestingly, macrophages decreased in inflammatory corneas after CXL, which should contribute to the regression of pathologic BVs and LVs in corneas, as macrophages play a key role in the induction of angiogenesis44, 45 and lymphangiogenesis46, 47, 48, 49 under pathological conditions in the cornea and in the maintenance of LVs 50. Furthermore, we also observed significant reduction in CD45 + leukocytes in suture‐induced inflammation in corneas after CXL treatment using riboflavin and UVA.…”

Section: Discussionmentioning

confidence: 52%

UV light crosslinking regresses mature corneal blood and lymphatic vessels and promotes subsequent high-risk corneal transplant survival

Hou

Tóth

et al. 2018

American Journal of Transplantation

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Immunologic graft rejection is the main complication after corneal transplant into pathologically prevascularized so‐called high‐risk eyes. The aim of this study was to evaluate whether ultraviolet (UV) light crosslinking can regress pathologic corneal blood and lymphatic vessels and thereby improve subsequent graft survival. Using the murine model of suture‐induced corneal neovascularization, we found that corneal crosslinking with UVA light and riboflavin regressed both preexisting blood and lymphatic vessels significantly via induction of apoptosis in vascular endothelial cells. In addition, macrophages and CD45+ cell counts were significantly reduced. Consistently, corneal crosslinking reduced keratocyte density and corneal thickness without affecting corneal nonvascular endothelial cells, iris, and lens depending on the crosslinking duration. Furthermore, using the murine model of corneal transplant, long‐term graft survival was significantly promoted (P < .05) and CD4+ CD25+FoxP3+ T regulatory cells were upregulated (P < .01) in high‐risk eyes preoperatively treated with crosslinking. Our results suggest UV light crosslinking as a novel method to regress both pathologic corneal blood and lymphatic vessels and to reduce CD45+ inflammatory cells. Furthermore, this study demonstrates for the first time that preoperative corneal crosslinking in prevascularized high‐risk eyes can significantly improve subsequent graft survival and may become a promising novel therapy in the clinic.

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Section: Discussionmentioning

confidence: 52%

UV light crosslinking regresses mature corneal blood and lymphatic vessels and promotes subsequent high-risk corneal transplant survival

Hou

Tóth

et al. 2018

American Journal of Transplantation

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“…The low PF-L is undoubtedly due to the inability of the methodology to accurately detect all dividing LECs within tumours, and is most probably underestimated as sprouting of new vessels begins at different levels along the lymphatic vessel [44]. Furthermore, new vessels may originate from circulating progenitors or from non-endothelial cells via trans-differentiation [45]. Intriguingly the presence of large number of lymphatics in tumour areas which were densely infiltrated by inflammatory cells was noted.…”

Section: Discussionmentioning

confidence: 99%

Lymphatic and angiogenic characteristics in breast cancer: morphometric analysis and prognostic implications

Mohammed

Ellis

Elsheikh

et al. 2008

Breast Cancer Res Treat

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Controversy exists regarding the topography of lymph vessels in breast cancer, their usefulness as prognostic factors, relationship with angiogenesis and whether active lymphangiogenesis occurs within the tumour. A series of 177 well-characterized breast cancers, with long term follow up, were stained with D2-40, CD31 and CD34. Distribution of lymphatics and lymph vessel density (LVD) were assessed in three areas, intratumoural, peripheral and peritumoural and correlated with clinicopathological criteria and patient prognosis. Microvessel density (MVD) was assessed and correlated with LVD. Double immunohistochemical staining with D2-40 and MIB-1 was carried out to assess the proliferative status of lymphatics and of the tumour emboli within. Peritumoural lymphatics were detected in all tumours whereas peripheral and intratumoural lymphatics were detected in 86 and 41% of specimens, respectively. Tumours with higher total LVD were significantly associated with the presence of lymph node (LN) metastasis and shorter overall survival (OS). In multivariate analysis, tumour grade, LN status and the presence of lymphovascular invasion, but not LVD, were independent poor prognostic factors. No association was found between LVD and MVD. Proliferating lymphatics were detected in 29% of specimens and were significantly associated with dense inflammatory infiltrate. In conclusion, lymphatics are located primarily in the peritumoural and peripheral areas in breast cancer and seem to play an important role in disease progression by being routes for tumour dissemination. The lack of correlation between lymphangiogenic and angiogenic characteristics suggests two distinct processes and the presence of active lymphangiogenesis, albeit in a small portion of specimens, may have important therapeutic implications.Keywords Angiogenesis Á Breast cancer Á D2-40 Á Lymphangiogenesis and prognosis Introduction and aims

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“…Macrophages are able to trigger lymphangiogenesis via two pathways: either by release of VEGF-C or by metamorphosis into lymphatic endothelial cells (Maruyama et al, 2005). The paraffin slides were immunolabeled with anti-CD68 to determine the number of infiltrating macrophages.…”

Section: Higher Occurrence Of Macrophages In MM Kidneysmentioning

confidence: 99%

Lymphangiogenesis Is Upregulated in Kidneys of Patients With Multiple Myeloma

Zimmer

Dahdal

Mühlfeld

et al. 2010

The Anatomical Record

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Neolymphangiogenesis has recently been demonstrated in transplanted kidneys as well as in chronic interstitial nephritis and IgA nephropathy. However, its significance in kidney disease remains to be defined and a systematic study of renal lymphangiogenesis is warranted. We investigated patients with multiple myeloma (MM) presenting in the great majority with acute renal insufficiency. Controls were allograft kidney donors and patients with renal insufficiency due to acute renal failure (ARF). Lymph vessel length density (LVD) was quantified immunohistochemically by means of antipodoplanin staining followed by computer-assisted stereology. The mean LVD in kidneys of patients with MM (23.19 mm À2 ) was higher when compared with allograft donors (7.42 mm À2 , P ¼ 0.0003) and patients with ARF (6.78 mm À2 , P ¼ 0.0002). The higher LVD was significantly associated with interstitial inflammation, and the newly formed lymph vessels were accompanied by diffuse and nodular interstitial infiltrates composed mainly of CD20 þ B cells and CD27 þ plasma cells. The infiltrates in patients with MM also displayed a higher expression of the B-cell chemoattractant CXCL13. These results demonstrate for the first time that lymphangiogenesis is a prominent feature in MM kidneys and that it is associated with a significant accumulation of macrophages, CD20 þ and CD27 þ B lymphocytes. Further studies should clarify whether these changes represent a beneficial or detrimental factor in the progression of the myeloma-related kidney damage. Anat Rec, 293:1497Rec, 293: -1505

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Inflammation-induced lymphangiogenesis in the cornea arises from CD11b-positive macrophages

Cited by 633 publications

References 36 publications

UV light crosslinking regresses mature corneal blood and lymphatic vessels and promotes subsequent high-risk corneal transplant survival

UV light crosslinking regresses mature corneal blood and lymphatic vessels and promotes subsequent high-risk corneal transplant survival

Lymphatic and angiogenic characteristics in breast cancer: morphometric analysis and prognostic implications

Lymphangiogenesis Is Upregulated in Kidneys of Patients With Multiple Myeloma

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