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

J Clin Invest. 2005 Sep;115(9):2363-72. doi: 10.1172/JCI23874.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD11b Antigen / immunology*
  • Cornea / cytology
  • Cornea / immunology*
  • Cornea / pathology*
  • Cornea / physiology
  • Corneal Transplantation
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism
  • Glycoproteins / metabolism
  • Inflammation / metabolism*
  • Lymphangiogenesis / physiology*
  • Macrophages / cytology
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Male
  • Membrane Glycoproteins / metabolism
  • Membrane Transport Proteins
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, SCID
  • Mice, Transgenic
  • Neovascularization, Physiologic / physiology
  • Promoter Regions, Genetic
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism

Substances

  • CD11b Antigen
  • Glycoproteins
  • Gp38 protein, mouse
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Recombinant Fusion Proteins
  • Xlkd1 protein, mouse