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Published ahead of print on August 14, 2003, doi:10.1165/rcmb.2003-0208OC

Am. J. Respir. Cell Mol. Biol., Volume 30, Number 2, February 2004, 220-227

A more recent version of this article appeared on February 1, 2004
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Submitted on June 2, 2003
Revised on August 12, 2003

Trafficking of Th1 Cells to Lung: A Role for Selectins and a PSGL-1 Independent Ligand

Joan G Clark1*, Janis B Mandac-Dy2, Anne E Dixon2, David K Madtes1, Kristin M Burkhart2, John M Harlan3, and Daniel C Bullard4

1 Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA, USA; Fred Hutchinson Cancer Research Center, Seattle, WA, USA, 2 Fred Hutchinson Cancer Research Center, Seattle, WA, USA, 3 Division of Hematology, University of Washington, Seattle, WA, USA, 4 Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA

* To whom correspondence should be addressed. 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 (PSGL-1), which was functional in binding to P-and E-selectin in vitro. However, our studies reveal that a ligand distinct from PSGL-1 also binds these selectins in vitro and appears to play a physiologic role in in vivo emigration of Th1 lymphocytes into the lung.




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