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A murine model to study leukocyte rolling and intravascular trafficking in lung microvessels.

Sikora, Lyudmila ; Johansson, Åsa C M LU ; Rao, Savita P. ; Hughes, Greg ; Brodie, David H and Sriramarao, Pragada (2003) In American Journal of Pathology 162(6). p.2019-2028
Abstract
The cascade of leukocyte interactions under conditions of blood flow is well established in the systemic microcirculation, but not in lung microcirculation. We have developed a murine model to study lung microcirculation by transplanting lung tissue into dorsal skin-fold window chambers in nude mice and examining the ability of leukocytes to traffic within revascularized lung microvessels by intravital microscopy. The revascularized lung allograft demonstrated a network of arterioles, capillaries, and postcapillary venules with continuous blood flow. Stimulation of the lung allograft with TNF-alpha induced leukocyte rolling and adhesion in both arterioles and venules. Treatment with function-blocking anti-selectin mAb revealed that P- and... (More)
The cascade of leukocyte interactions under conditions of blood flow is well established in the systemic microcirculation, but not in lung microcirculation. We have developed a murine model to study lung microcirculation by transplanting lung tissue into dorsal skin-fold window chambers in nude mice and examining the ability of leukocytes to traffic within revascularized lung microvessels by intravital microscopy. The revascularized lung allograft demonstrated a network of arterioles, capillaries, and postcapillary venules with continuous blood flow. Stimulation of the lung allograft with TNF-alpha induced leukocyte rolling and adhesion in both arterioles and venules. Treatment with function-blocking anti-selectin mAb revealed that P- and L-selectin are the predominant rolling receptors in the lung microvessels, with E-selectin strengthening P-selectin-dependent interactions. Intravital microscopic studies also demonstrated that during their transit in capillaries, some leukocytes undergo shape change and continue to roll as elongated cells in postcapillary venules. Furthermore, the revascularized microvessels demonstrated the ability to undergo vasoconstriction in response to superfusion with endothelin-1. Overall, these studies demonstrate that the revascularized lung allograft is responsive to various external stimuli such as cytokines and vaso-active mediators and serves as a model to evaluate the interaction of leukocytes with the vascular endothelium in the lung microcirculation under acute as well as chronic experimental conditions. (Less)
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author
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publishing date
type
Contribution to journal
publication status
published
in
American Journal of Pathology
volume
162
issue
6
pages
2019 - 2028
publisher
American Society for Investigative Pathology
external identifiers
  • scopus:0038582589
ISSN
1525-2191
DOI
10.1016/S0002-9440(10)64334-9
language
English
LU publication?
no
id
4d8d003a-ed5d-4257-88ba-6ac9ffdee8a2
date added to LUP
2024-06-05 11:11:57
date last changed
2024-06-06 04:02:25
@article{4d8d003a-ed5d-4257-88ba-6ac9ffdee8a2,
  abstract     = {{The cascade of leukocyte interactions under conditions of blood flow is well established in the systemic microcirculation, but not in lung microcirculation. We have developed a murine model to study lung microcirculation by transplanting lung tissue into dorsal skin-fold window chambers in nude mice and examining the ability of leukocytes to traffic within revascularized lung microvessels by intravital microscopy. The revascularized lung allograft demonstrated a network of arterioles, capillaries, and postcapillary venules with continuous blood flow. Stimulation of the lung allograft with TNF-alpha induced leukocyte rolling and adhesion in both arterioles and venules. Treatment with function-blocking anti-selectin mAb revealed that P- and L-selectin are the predominant rolling receptors in the lung microvessels, with E-selectin strengthening P-selectin-dependent interactions. Intravital microscopic studies also demonstrated that during their transit in capillaries, some leukocytes undergo shape change and continue to roll as elongated cells in postcapillary venules. Furthermore, the revascularized microvessels demonstrated the ability to undergo vasoconstriction in response to superfusion with endothelin-1. Overall, these studies demonstrate that the revascularized lung allograft is responsive to various external stimuli such as cytokines and vaso-active mediators and serves as a model to evaluate the interaction of leukocytes with the vascular endothelium in the lung microcirculation under acute as well as chronic experimental conditions.}},
  author       = {{Sikora, Lyudmila and Johansson, Åsa C M and Rao, Savita P. and Hughes, Greg and Brodie, David H and Sriramarao, Pragada}},
  issn         = {{1525-2191}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{2019--2028}},
  publisher    = {{American Society for Investigative Pathology}},
  series       = {{American Journal of Pathology}},
  title        = {{A murine model to study leukocyte rolling and intravascular trafficking in lung microvessels.}},
  url          = {{http://dx.doi.org/10.1016/S0002-9440(10)64334-9}},
  doi          = {{10.1016/S0002-9440(10)64334-9}},
  volume       = {{162}},
  year         = {{2003}},
}