0000000000179254

AUTHOR

Timothy W. Secomb

0000-0002-0176-5502

Intussusceptive Remodeling of Vascular Branch Angles in Chemically-Induced Murine Colitis

Intussusceptive angiogenesis is a developmental process linked to both blood vessel replication and remodeling in development. To investigate the prediction that the process of intussusceptive angiogenesis is associated with vessel angle remodeling in adult mice, we systematically evaluated corrosion casts of the mucosal plexus in mice with trinitrobenzesulphonic acid (TNBS)-induced and dextran sodium sulfate (DSS)-induced colitis. The mice demonstrated a significant decrease in vessel angles in both TNBS-induced and DSS-induced colitis within 4 weeks of the onset of colitis (p<.001). Corrosion casts 28–30 days after DSS treatment were studied for a variety of detailed morphometric changes.…

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Microangiectasias: Structural regulators of lymphocyte transmigration

The migration of lymphocytes into inflammatory tissue requires the migrating cell to overcome mechanical forces produced by blood flow. A generally accepted hypothesis is that these forces are overcome by a multistep sequence of adhesive interactions between lymphocytes and endothelial cells. This hypothesis has been recently challenged by results demonstrating wall shear stress on the order of 20 dyn/cm 2 in vivo and infrequent lymphocyte–endothelial adhesion at wall shear stress &gt;1–2 dyn/cm 2 in vitro . Here, we show that lymphocyte slowing and transmigration in the skin is associated with microangiectasias, i.e., focal structural dilatations of microvessel segments. Microangiectasias…

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Inflammation-Induced Intussusceptive Angiogenesis in Murine Colitis

Intussusceptive angiogenesis is a morphogenetic process that forms new blood vessels by the division of a single blood vessel into two lumens. Here, we show that this process of intraluminal division participates in the inflammation-induced neovascularization associated with chemically induced murine colitis. In studies of both acute (4-7 days) and chronic (28-31 days) colitis, intravital microscopy of intravascular tracers demonstrated a twofold reduction in blood flow velocity. In the acute colitis model, the decreased velocity was associated with marked dilatation of the mucosal plexus. In contrast, chronic inflammation was associated with normal caliber vessels and duplication (and trip…

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Focal topographic changes in inflammatory microcirculation associated with lymphocyte slowing and transmigration

Microcirculation is the primary mechanism for delivering lymphocytes to inflammatory tissues. Blood flow within microvessels ensures a supply of lymphocytes at the blood-endothelial interface. Whether the structure of the inflammatory microcirculation facilitates lymphocyte transmigration is less clear. To illuminate the microcirculatory changes associated with lymphocyte transmigration, we used intravital videomicroscopy to examine the dermal microcirculation after application of the epicutaneous antigen oxazolone. Intravascular injection of fluorescein-labeled dextran demonstrated focal topographic changes in the microcirculation. These focal changes had the appearance of loops or hairpin…

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