| Leukocyte adhesion -
molecular mechanisms
Department
of Biosciences Leukocyte adhesion is of pivotal importance in leukocyte physiology. If leukocytes cannot adhere to other leukocytes or various target cells, B lymphocytes cannot synthesize immunoglobulins, T and natural killer cells are not cytotoxic, and neutrophils show no phagocytosis or chemotaxis. Furthermore, the leukocytes cannot bind to endothelial cells and induce inflammation. Several leukocyte adhesion molecules have been described among the most important of which are the leukocyte-specific §2-integrins, the intercellular adhesion molecules (ICAM) and the carbohydrate-binding selectins. The group has focused on the structure and binding regions in ICAMs (especially ICAM-2) and on the mechanisms of activation of leukocyte adhesion. The group has recently identified two novel ICAMs, ICAM-4 and ICAM-5. ICAM-4 (Landsteiner-Wiener antigen) is found only on red cells. ICAM-5 (telencephalin) is expressed in the telencephalon region of the brain. These molecules have been extensively studied, we have mapped the binding regions, determined to what leukocyte integrins they bind etc. In neither case is the physiological function known. ICAM-4 is possibly important in red cell turnover, for the retention of immature erythroid cells in the bone marrow or uptake in spleen. The role of telencephalin could be in binding microglial cells but other possibilities certainly exist. Another important project is the functional role of phosphorylation of integrins. We have recently identified a strong threonine phosphorylation in the integrin §2-chain. We have now made various phosphorylated peptides from the §2-chain and are studying their interactions with various cytoskeletal components. Personnel Matti Autero, Ph. D.; Erkki Koivunen, Ph.D.; Susanna Fagerholm, M.Sc.; Eveliina Ihanus, M.Sc.; Cami Kantor-Aaltonen, Ph.Lic.; Annika Kotovuori, M.Sc.; Pekka Kotovuori, M.Sc.; Heli Lehtokangas, student; Seija Taube, student, Li Tian, M.Med.; Martti Tolvanen, Ph.Lic.; Leena Valmu, Ph.Lic.; Leena Kuoppasalmi, technician. Selected publications Li, R., Nortamo, P., Valmu, L., Tolvanen, M., Huuskonen, J., Kantor, C. and Gahmberg, C. G. J. Biol. Chem., 268:17513-17518, 1993. Li, R., Nortamo, P., Kantor, C., Kovanen, P., Timonen, T. and Gahmberg, C. G. J. Biol. Chem., 268:21474-21477, 1993. Sato, T., Furukawa, K., Autero, M., Gahmberg, C. G. and Kobata, A. Biochemistry, 32:12694-12704, 1993. Autero, M., Saharinen, J., Pessa-Morikawa, T., Soula-Rothhut, M., Oetken, C., Gassmann, M., Bergman, M., Alitalo, K., Burn, P., Gahmberg, C. G. and Mustelin, T. Mol. Cell. Biol., 14:1308-1321, 1994. Li, R., Xie, J., Kantor, C., Koistinen, V., Altieri, D. C., Nortamo, P. and Gahmberg, C. G. J. Cell Biol., 129:1143-1153, 1995. Ylänne, J., Huuskonen, J., O'Toole, T. E., Ginsberg, M. H., Virtanen, I. and Gahmberg, C. G. J. Biol. Chem., 270:9550-9557, 1995. Valmu, L. and Gahmberg, C. G. 1995. J. Immunol., 155:1175-1183, 1995. Heiska, L., Kantor, C., Parr, T., Critchley, D. R., Vilja, P., Gahmberg, C. G. and Carpén, O. J. Biol. Chem., 271:26214-26219, 1996. Gahmberg, C. G. and Tolvanen, M. Trends Biochem. Sci., 21:308-311, 1996. Tian, L., Yoshihara, Y., Mizuno, T., Mori, K. and Gahmberg, C. G. J. Immunol., 158:928-936, 1997. Gahmberg, C. G., Tolvanen, M. and Kotovuori, P. Eur. J. Biochem., 245:215- 232, 1997. Furukawa, K., Funakoshi, Y., Autero, M., Horejsi, V., Kobata, A. and Gahmberg, C. G. Eur. J. Biochem., 251:288-294, 1998. Funding Academy of Finland, Sigrid Jusélius Foundation, The Finnish Cancer Society. |
| Last update 01.07.1998 | Maintained by Jari Ylänne (ylanne@csc.fi) |