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Published ahead of print on August 14, 2003, doi:10.1165/rcmb.2003-0208OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 30, pp. 220-227, 2004
© 2004 American Thoracic Society
DOI: 10.1165/rcmb.2003-0208OC

Trafficking of Th1 Cells to Lung

A Role for Selectins and a P-Selectin Glycoprotein-1–Independent Ligand

Joan G. Clark, Janis B. Mandac-Dy, Anne E. Dixon, David K. Madtes, Kristin M. Burkhart, John M. Harlan and Daniel C. Bullard

Division of Pulmonary and Critical Care Medicine, and Division of Hematology, Department of Medicine, University of Washington, Seattle; Fred Hutchinson Cancer Research Center, Seattle, Washington; and Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama

Address correspondence to: Joan G. Clark, M.D., P.O. Box 19024 (D3–190), Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109. E-mail: jclark{at}fhcrc.org

Trafficking of lymphocytes to lung is a critical component of pulmonary immune defense and surveillance. Selectins, expressed on vascular endothelium, regulate T lymphocyte emigration into tissues, such as skin, but the role of the selectins in trafficking of T cells to lung has not been well characterized. Here, we used a model of lung inflammation induced by adoptive transfer of alloreactive Th1 cells to analyze the role of P- and E-selectin in Th1 cell trafficking to lung in vivo. We found that both P- and E-selectin play an important role in Th1 lymphocyte migration to lung. We confirmed that the Th1 cells express P-selectin glycoprotein ligand-1, which was functional in binding to P- and E-selectin in vitro. However, our studies reveal that a ligand distinct from P-selectin glycoprotein-1 also binds these selectins in vitro and appears to play a physiologic role in in vivo emigration of Th1 lymphocytes into the lung.

Abbreviations: 5-(and –6)-carboxyfluorescein diacetate, succimidyl ester, 5(6)-CFDA, SE • cutaneous lymphocyte-associated antigen, CLA • E-selectin ligand-1, ESL-1 • intercellular adhesion molecule-1, ICAM-1 • o-sialoglycoprotease, OSGP • P-selectin glycoprotein-1, PSGL-1






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