Trafficking of Th1 cells to lung: a role for selectins and a P-selectin glycoprotein-1-independent ligand.
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.
Clark
Joan G
JG
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington, Seattle, WA 98109, USA. jclark@fhcrc.org
Mandac-Dy
Janis B
JB
Dixon
Anne E
AE
Madtes
David K
DK
Burkhart
Kristin M
KM
Harlan
John M
JM
Bullard
Daniel C
DC
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009439:Neuraminidase / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D019087:Selectins / Q000378:metabolism*; D018417:Th1 Cells / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D011993:Recombinant Fusion Proteins; D019087:Selectins; D009439:Neuraminidase