A Murine Model to Study Leukocyte Rolling and Intravascular Trafficking in Lung Microvessels
Autor: | David H. Broide, Savita P. Rao, Lyudmila Sikora, P. Sriramarao, Greg K. Hughes, Åsa Johansson |
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Rok vydání: | 2003 |
Předmět: |
Male
Pulmonary Circulation Pathology medicine.medical_specialty Mice Nude Inflammation Leukocyte Rolling Pathology and Forensic Medicine Microcirculation Mice Venules Cell Adhesion Leukocytes medicine Animals Lung Mice Inbred BALB C Endothelin-1 Tumor Necrosis Factor-alpha business.industry Respiratory disease Hemodynamics Antibodies Monoclonal respiratory system medicine.disease Capillaries Arterioles P-Selectin medicine.anatomical_structure Animals Newborn Vasoconstriction Models Animal Immunology Blood Vessels Animal Model Endothelium Vascular medicine.symptom business Intravital microscopy Blood vessel |
Zdroj: | The American Journal of Pathology. 162:2019-2028 |
ISSN: | 0002-9440 |
DOI: | 10.1016/s0002-9440(10)64334-9 |
Popis: | 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. |
Databáze: | OpenAIRE |
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