Inflammation-induced Lymphangiogenesis in the Cornea Arises from CD11b-positive Macrophages

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2005 Sep 3

PMID 16138190

Citations 305

Authors

Kazuichi Maruyama

Masaaki Ii

Claus Cursiefen

David G Jackson

Hiroshi Keino

Minoru Tomita

Nico van Rooijen

Hideya Takenaka

Patricia A DAmore

Joan Stein-Streilein

Douglas W Losordo

J Wayne Streilein

Affiliations

Soon will be listed here.

Abstract

In the inflamed cornea, there is a parallel outgrowth of blood and lymphatic vessels into the normally avascular cornea. We tested whether adaptive and/or innate immune cells were actively involved in the genesis of new lymphatic vessels. Our results indicate that innate immune cells (CD11b+ macrophages, but not CD11c+ dendritic cells) physically contributed to lymphangiogenesis under pathological conditions and that bone marrow-derived CD11b+ macrophages expressed lymphatic endothelial markers such as LYVE-1 and Prox-1 under inflamed conditions in the corneal stromata of mice. Furthermore, blood vascular endothelial cells that expressed the Tie2 promoter did not contribute to newly formed lymphatic vessels under inflamed conditions. Our in vitro experiments demonstrated that CD11b+ macrophages alone were capable of forming tube-like structures that expressed markers of lymphatic endothelium such as LYVE-1 and podoplanin. The novel finding that CD11b+ macrophages are critical for the development of inflammation-dependent lymphangiogenesis in the eye suggests a new mechanism of lymphangiogenesis.

Citing Articles

No cell fate conversion of macrophages to endothelial cells after myocardial infarction.

Lu Z, Zhuang L, Zhang R, Chen K, Zhang H, Yan X J Mol Cell Cardiol Plus. 2025; 3():100028.

PMID: 39803362 PMC: 11708121. DOI: 10.1016/j.jmccpl.2022.100028.

A human-like model of aniridia-associated keratopathy for mechanistic and therapeutic studies.

Javidjam D, Moustardas P, Abbasi M, Dashti A, Rautavaara Y, Lagali N JCI Insight. 2024; 10(2).

PMID: 39625791 PMC: 11790027. DOI: 10.1172/jci.insight.183965.

Cancer and lymphatic marker FOXC2 drives wound healing and fibrotic tissue formation.

Granoski M, Fischer K, Hahn W, Sivaraj D, Kussie H, Quintero F Front Physiol. 2024; 15:1427113.

PMID: 39473610 PMC: 11518795. DOI: 10.3389/fphys.2024.1427113.

Podoplanin expressing macrophages and their involvement in tertiary lymphoid structures in mouse models of Sjögren's disease.

Hovd A, Nayar S, Smith C, Kanapathippillai P, Iannizzotto V, Barone F Front Immunol. 2024; 15:1455238.

PMID: 39355243 PMC: 11442383. DOI: 10.3389/fimmu.2024.1455238.

Nasim S, Bichsel C, Pinto A, Alexandrescu S, Kozakewich H, Bischoff J Angiogenesis. 2024; 27(4):931-941.

PMID: 39343803 DOI: 10.1007/s10456-024-09950-8.

References

Matsui K, Soleiman A, Meraner P, Poczewski H, Kalt R, Schaffner G . Podoplanin, novel 43-kd membrane protein of glomerular epithelial cells, is down-regulated in puromycin nephrosis. Am J Pathol. 1997; 151(4):1141-52. PMC: 1858024. View

Oh S, Jeltsch M, Birkenhager R, McCarthy J, Weich H, Christ B . VEGF and VEGF-C: specific induction of angiogenesis and lymphangiogenesis in the differentiated avian chorioallantoic membrane. Dev Biol. 1997; 188(1):96-109. DOI: 10.1006/dbio.1997.8639. View

Banerji S, Ni J, Wang S, Clasper S, Su J, Tammi R . LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan. J Cell Biol. 1999; 144(4):789-801. PMC: 2132933. DOI: 10.1083/jcb.144.4.789. View

Weninger W, Partanen T, Mayer C, Kowalski H, Mildner M, Pammer J . Expression of vascular endothelial growth factor receptor-3 and podoplanin suggests a lymphatic endothelial cell origin of Kaposi's sarcoma tumor cells. Lab Invest. 1999; 79(2):243-51. View

Wigle J, Chowdhury K, Gruss P, Oliver G . Prox1 function is crucial for mouse lens-fibre elongation. Nat Genet. 1999; 21(3):318-22. DOI: 10.1038/6844. View

Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M . Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med. 1999; 5(4):434-8. DOI: 10.1038/7434. View

Streilein J, Yamada J, Dana M, Ksander B . Anterior chamber-associated immune deviation, ocular immune privilege, and orthotopic corneal allografts. Transplant Proc. 1999; 31(3):1472-5. DOI: 10.1016/s0041-1345(99)00010-x. View

Takeuchi M, Alard P, Streilein J . TGF-beta promotes immune deviation by altering accessory signals of antigen-presenting cells. J Immunol. 1998; 160(4):1589-97. View

Soleiman A, Horvat R, Amann G, Kowalski H, Kerjaschki D . [Podoplanin--a specific marker for lymphatic endothelium expressed in angiosarcoma]. Verh Dtsch Ges Pathol. 2000; 83:270-5. View

10.

Sinzelle E, Duong van Huyen J, Braunberger E, Deloche A, Kerjaschki D, Bruneval P . Intrapericardial lymphangioma with podoplanin immunohistochemical characterization of lymphatic endothelial cells. Histopathology. 2000; 37(1):93-4. DOI: 10.1046/j.1365-2559.2000.00955-8.x. View

11.

Mimura T, Amano S, Usui T, Kaji Y, Oshika T, Ishii Y . Expression of vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 in corneal lymphangiogenesis. Exp Eye Res. 2001; 72(1):71-8. DOI: 10.1006/exer.2000.0925. View

12.

Skobe M, Hawighorst T, Jackson D, Prevo R, Janes L, Velasco P . Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med. 2001; 7(2):192-8. DOI: 10.1038/84643. View

13.

Prevo R, Banerji S, Ferguson D, Clasper S, Jackson D . Mouse LYVE-1 is an endocytic receptor for hyaluronan in lymphatic endothelium. J Biol Chem. 2001; 276(22):19420-30. DOI: 10.1074/jbc.M011004200. View

14.

Skobe M, Hamberg L, Hawighorst T, Schirner M, Wolf G, Alitalo K . Concurrent induction of lymphangiogenesis, angiogenesis, and macrophage recruitment by vascular endothelial growth factor-C in melanoma. Am J Pathol. 2001; 159(3):893-903. PMC: 1850477. DOI: 10.1016/S0002-9440(10)61765-8. View

15.

Jackson D . New molecular markers for the study of tumour lymphangiogenesis. Anticancer Res. 2002; 21(6B):4279-83. View

16.

Wigle J, Harvey N, Detmar M, Lagutina I, Grosveld G, Gunn M . An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype. EMBO J. 2002; 21(7):1505-13. PMC: 125938. DOI: 10.1093/emboj/21.7.1505. View

17.

Cursiefen C, Schlotzer-Schrehardt U, Kuchle M, Sorokin L, Alitalo K, Jackson D . Lymphatic vessels in vascularized human corneas: immunohistochemical investigation using LYVE-1 and podoplanin. Invest Ophthalmol Vis Sci. 2002; 43(7):2127-35. View

18.

Schoppmann S, Birner P, Stockl J, Kalt R, Ullrich R, Caucig C . Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis. Am J Pathol. 2002; 161(3):947-56. PMC: 1867252. DOI: 10.1016/S0002-9440(10)64255-1. View

19.

Hong Y, Harvey N, Noh Y, Schacht V, Hirakawa S, Detmar M . Prox1 is a master control gene in the program specifying lymphatic endothelial cell fate. Dev Dyn. 2002; 225(3):351-7. DOI: 10.1002/dvdy.10163. View

20.

Chang L, Kaipainen A, Folkman J . Lymphangiogenesis new mechanisms. Ann N Y Acad Sci. 2003; 979:111-9. DOI: 10.1111/j.1749-6632.2002.tb04872.x. View