Unresolved Questions

Postcapillary venules are formidable machines for leukocyte recruitment. More than 90 percent of all neutrophils in capillaries begin rolling in postcapillary venules, and more than 90 percent of rolling leukocytes (neutrophils) arrest successfully in cytokine-activated venules. Yet, the overall extraction efficiency during inflammation is less than 50 percent, suggesting that some arresting neutrophils may detach again, or that transmigration may be inefficient. This process is not understood at the quantitative level. The role of the endothelial surface glycocalyx is just beginning to be explored. Rolling, arrest, and transmigration of many lymphocyte subsets including activated Th1 and Th2 CD4 helper cells, CD8 cytotoxic cells, natural killer cells, gd T cells, and NKT cells have not been studied in vivo. Very little is known about eosinophil and basophil recruitment and the resolution of inflammation, a process that likely also involves cell interactions in postcapillary venules. Finally, the mechanisms mentioned previously are valid for some tissues, but not the lungs, liver, spleen, kidney, or brain. Suitable intravital microscopy systems and other models need to be developed to address these issues.


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6a. Dunne, J. L., Collins, R. G., Beaudet, A. L., Ballantyne, C. M., and Ley, K. (2003) Mac-1, but not LFA-1, uses intercellular adhesion molecule-1 to mediate slow leukocyte rolling in TNF-alpha-induced inflammation. J. Immunol. 171, 6105-6111.

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9. Campbell, J. J., Hedrick, J., Zlotnik, A., Siani, M. A., Thompson, D. A., and Butcher, E. C. (1998). Chemokines and the arrest of lymphocytes rolling under flow conditions. Science 279, 381-384. Discovery of arrest chemokines.

Capsule Biography

Dr. Ley has headed the Cardiovascular Research Center at the University of Virginia since 2001 and was the winner of the 1986 Abbott Microcirculation Award and the 2001 Curt A. Wiederhielm Award of the Microcirculatory Society. His laboratory primarily focuses on inflammatory processes in the microcirculation, in atherosclerosis and inflammatory bowel disease. His work is supported by grants from the NIH.

Cell Adhesion Molecules: Structure, Function, Organization, and Role in Leukocyte Trafficking through the Lung

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