Cell-Surface Glycoconjugates Controlling Human T-Lymphocyte Homing: Implications for Bronchial Asthma and Atopic Dermatitis
Cell-surface glycans play important roles in lymphocyte traffic and homing. Cell adhesion mediated by glycans, such as selectin-mediated cell adhesion, is involved in the first step of every process of extravasation of leukocytes, either in granulocytes or in lymphocytes (Fig. 1). Glycan-mediated cell adhesion is virtually an only one cell-adhesion system that tolerates a strong shear force of normal blood flow in the general circulation. This step is crucial for every leukocyte diapedesis; without glycan-mediated cell adhesion, other secondary proteinaceous cell-adhesion molecules such as integrins or the Ig superfamily do not operate effectively. Recently, it has become increasingly clear that homing processes of various subsets of T lymphocytes are elegantly regulated by different species of cell-adhesive glycans, and alterations in glycan expression are closely associated with the pathophysiology of several well-known human diseases.
KeywordsAtopic Dermatitis Sialic Acid Peripheral Lymph Node High Endothelial Venule Selectin Ligand
This work was supported in part by grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology (24590364 and on innovative areas 23112520), grants-in-aid for young scientists from the Japan Society for the Promotion of Science (20790583 and 22790774), grants-in-aid for the Third-Term Comprehensive Ten-year Strategy for Cancer Control from the Ministry of Health and Welfare, and a grant from the Uehara Memorial Foundation, Japan.
- 4.Mitsuoka C, Sawada-Kasugai M, Ando-Furui K, Izawa M, Nakanishi H, Nakamura S, Ishida H, Kiso M, Kannagi R (1998) Identification of a major carbohydrate capping group of the L-selectin ligand on high endothelial venules in human lymph nodes as 6-sulfo sialyl Lewis x. J Biol Chem 273:11225–11233CrossRefPubMedGoogle Scholar
- 5.Kimura N, Mitsuoka C, Kanamori A, Hiraiwa N, Uchimura K, Muramatsu T, Tamatani T, Kansas GS, Kannagi R (1999) Reconstitution of functional L-selectin ligands on a cultured human endothelial cell line by co-transfection of α1 → 3 fucosyltransferase VII and newly cloned GlcNAcβ 6-sulfotransferase cDNA. Proc Natl Acad Sci USA 96:4530–4535CrossRefPubMedGoogle Scholar
- 20.Izawa M, Kumamoto K, Mitsuoka C, Kanamori A, Ohmori K, Ishida H, Nakamura S, Kurata-Miura K, Sasaki K, Nishi T, Kannagi R (2000) Expression of sialyl 6-sulfo Lewis x is inversely correlated with conventional sialyl Lewis x expression in human colorectal cancer. Cancer Res 60:1410–1416PubMedGoogle Scholar