Vascular microarchitecture of murine colitis-associated lymphoid angiogenesis

Anat Rec (Hoboken). 2009 May;292(5):621-32. doi: 10.1002/ar.20902.


In permissive tissues, such as the gut and synovium, chronic inflammation can result in the ectopic development of anatomic structures that resemble lymph nodes. These inflammation-induced structures, termed lymphoid neogenesis or tertiary lymphoid organs, may reflect differential stromal responsiveness to the process of lymphoid neogenesis. To investigate the structural reorganization of the microcirculation involved in colonic lymphoid neogenesis, we studied a murine model of dextran sodium sulfate (DSS)-induced colitis. Standard 2-dimensional histology demonstrated both submucosal and intramucosal lymphoid structures in DSS-induced colitis. A spatial frequency analysis of serial histologic sections suggested that most intramucosal lymphoid aggregates developed de novo. Intravital microscopy of intravascular tracers confirmed that the developing intramucosal aggregates were supplied by capillaries arising from the quasi-polygonal mucosal plexus. Confocal optical sections and whole mount morphometry demonstrated capillary networks (185 +/- 46 microm diameter) involving six to ten capillaries with a luminal diameter of 6.8 +/- 1.1 microm. Microdissection and angiogenesis PCR array analysis demonstrated enhanced expression of multiple angiogenic genes including CCL2, CXCL2, CXCL5, Il-1b, MMP9, and TNF within the mucosal plexus. Intravital microscopy of tracer particle flow velocities demonstrated a marked decrease in flow velocity from 808 +/- 901 microm/sec within the feeding mucosal plexus to 491 +/- 155 microm/sec within the capillary structures. We conclude that the development of ectopic lymphoid tissue requires significant structural remodeling of the stromal microcirculation. A feature of permissive tissues may be the capacity for lymphoid angiogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Capillaries / metabolism
  • Capillaries / pathology*
  • Capillaries / physiopathology
  • Chemokines / analysis
  • Chemokines / metabolism
  • Colitis, Lymphocytic / chemically induced
  • Colitis, Lymphocytic / pathology*
  • Colitis, Lymphocytic / physiopathology
  • Coloring Agents
  • Cytokines / analysis
  • Cytokines / metabolism
  • Dextran Sulfate / toxicity
  • Disease Models, Animal
  • Intestinal Mucosa / blood supply
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Lymphoid Tissue / blood supply*
  • Lymphoid Tissue / metabolism
  • Lymphoid Tissue / pathology*
  • Matrix Metalloproteinases / analysis
  • Matrix Metalloproteinases / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microcirculation / physiology*
  • Microscopy, Confocal
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology*
  • Neovascularization, Pathologic / physiopathology
  • Regional Blood Flow / physiology
  • Staining and Labeling / methods


  • Chemokines
  • Coloring Agents
  • Cytokines
  • Dextran Sulfate
  • Matrix Metalloproteinases