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, ex- pressed on vascular endothelium, regulate T lymphocyte emigra- tion 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. The regulated trafficking of lymphocytes from the blood- stream to lung is a critical component of pulmonary immune surveillance and host defense. Localization of lymphocytes within the vasculature involves a stepwise interaction be- tween molecules on the surface of lymphocytes and adhe- sion molecules on endothelium (1-5). Primary adhesion of lymphocytes may occur through members of the selectin family (i.e., P-, E-, and L-selectin) and their carbohydrate ligands on various glycoproteins such as P-selectin glycopro- tein ligand-1 (PSGL-1), CD34, cutaneous lymphocyte-associ- ated antigen (CLA), and E-selectin ligand-1 (ESL-1) (6-9). The selectins clearly are involved in lymphocyte homing to lymphoid tissue and skin (3, 10). The importance of this mechanism in lung lymphocyte interactions in the pulmo- nary microvasculature is not clear, but a role for selectins in margination of neutrophils in noncapillary microvessels of lung has been demonstrated (11). During lymphocyte recruitment to lung in response to particulate antigen in a murine model, P- and E-selectin expression was increased (12). Trafficking of cultured T lymphocytes to lung 2 d after intratracheal challenge with particulate antigen was reduced by deficiency of the T cell enzyme ( (1, 3)-fucosyltransfer-