Inflammation-induced lymphangiogenesis in the cornea arises from CD11b-positive macrophages.
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.
Maruyama
Kazuichi
K
Ocular Immunology Group, The Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.
Ii
Masaaki
M
Cursiefen
Claus
C
Jackson
David G
DG
Keino
Hiroshi
H
Tomita
Minoru
M
Van Rooijen
Nico
N
Takenaka
Hideya
H
D'Amore
Patricia A
PA
Stein-Streilein
Joan
J
Losordo
Douglas W
DW
Streilein
J Wayne
JW
D000818:Animals; D039481:CD11b Antigen / Q000276:immunology*; D003315:Cornea / Q000166:cytology / Q000276:immunology* / Q000473:pathology* / Q000502:physiology; D016039:Corneal Transplantation; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism*; D042583:Lymphangiogenesis / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000502:physiology; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000098853:Podoplanin
D039481:CD11b Antigen; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D011993:Recombinant Fusion Proteins; C490441:Pdpn protein, mouse; D000098853:Podoplanin; C492273:LYVE1 protein, mouse