The carbohydrate portions of cell membrane glycolipids and glycoproteins are important in both the function and immunologic recognition of cells. Both cell- and tissue-specific complex carbohydrates exist and many cell- and tissue-specific monoclonal antibodies are found to be directed against these moeities.
The aims of this work are to isolate and chemically characterize these complex carbohydrate moeities of human white blood cell membrane glycolipids and glycoproteins and to determine their immunologic and functional roles. This will be accomplished by acquiring large numbers of cells from leukapheresis of normal persons and persons with various leukemias. Isolation of the molecules will be done and chemical analysis will be performed using column chromatography, gas-liquid and high-pressure liquid chromatography and mass spectrometry. Enzyme hydrolysis will be done to confirm the sequences. Immunologic studies will be done using polyclonal and monoclonal antibodies directed against normal and leukemic cells, and methods will include immunoblotting, radial immunodiffusion and cytofluorometry. Functional studies will be done utilizing isolated glycopeptides and glycolipids (and antibodies to them) in several in vitro systems such as assays for adhesion, killing, oxygen radical generation, and phagocytosis for granulocytes. For lymphoid cells aasays will include lymphokine production, allogeneic immunologic response, and phenotypic typing. These studies are important to our understanding of the nature of leukocyte and leukemia-specific antigens and to the functions of human leukocyte cell surface glycoproteins. They will also greatly improve our understanding of the role that surface glycoproteins and glycolipids play in the development and maintenance of the leukemia cell phenotype. (AG)
| Fukuda, M; Carlsson, S R; Klock, J C et al. (1986) Structures of O-linked oligosaccharides isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells. J Biol Chem 261:12796-806 |
| Fukuda, M N; Dell, A; Oates, J E et al. (1985) Structures of glycosphingolipids isolated from human granulocytes. The presence of a series of linear poly-N-acetyllactosaminylceramide and its significance in glycolipids of whole blood cells. J Biol Chem 260:1067-82 |
