title: Binding of L-selectin to its vascular and extravascular ligands is differentially regulated by pH.
abstract: Ligands for L-selectin, a leukocyte adhesion molecule, are expressed in high endothelial venules (HEVs) in lymph nodes and extravascular tissues, such as renal tubules. Here, we report that the binding of L-selectin to its vascular and extravascular ligands is differentially regulated by pH. The optimal L-selectin-dependent binding of leukocytes to HEVs was observed at pH 7.4, a physiological pH in the blood. In contrast, the optimal binding of leukocytes to the renal tubules was observed at pH 5.6. Consistently, optimal binding of soluble recombinant L-selectin to a major vascular ligand, 6-sulfo sialyl Lewis X, was observed at pH 7.4. Binding to extravascular ligands, such as chondroitin sulfate (CS) B, CS E and heparan sulfate, occurred at pH 5.6. Under physiological shear stress ranging from 1 to 2 dynes/cm(2), maximal leukocyte rolling on vascular ligands was observed at pH 6.8 to 7.4, and no rolling was detected at pH conditions below 5.6. These findings suggest that the pH environment is one important factor that determines leukocyte trafficking under physiological and pathological conditions.
authors: Division of Translational and Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa 920-0934, Japan.
authors: Mayumi
authors: M
authors: Hirose
authors: Ryuji
authors: R
authors: Matsumura
authors: Kaori
authors: K
authors: Sato
authors: Toshiyuki
authors: T
authors: Murai
authors: Hiroto
authors: H
authors: Kawashima
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000502:physiology; D002448:Cell Adhesion; D003871:Dermatan Sulfate / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D019041:L-Selectin / Q000378:metabolism*; D036904:Leukocyte Rolling; D007962:Leukocytes / Q000378:metabolism / Q000502:physiology*; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D003871:Dermatan Sulfate; D006497:Heparan Sulfate; D019041:L-Selectin; D008024:Ligands