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Vascular Microarchitecture of Murine Colitis‐Associated Lymphoid Angiogenesis
Author(s) -
Turhan Aslihan,
Lin Miao,
Lee Grace S.,
Miele Lino F.,
Tsuda Akira,
Konerding Moritz A.,
Mentzer Steven J.
Publication year - 2009
Publication title -
the anatomical record: advances in integrative anatomy and evolutionary biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.678
H-Index - 62
eISSN - 1932-8494
pISSN - 1932-8486
DOI - 10.1002/ar.20902
Subject(s) - pathology , lymphatic system , angiogenesis , intravital microscopy , microcirculation , neogenesis , stromal cell , lymphangiogenesis , biology , inflammation , medicine , immunology , cancer research , genetics , islet , cancer , insulin , metastasis , endocrinology
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 μm diameter) involving six to ten capillaries with a luminal diameter of 6.8 ± 1.1 μm. 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 μm/sec within the feeding mucosal plexus to 491 ± 155 μm/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. Anat Rec, 292:621–632, 2009. © 2009 Wiley‐Liss, Inc.