Ultrastructural modulations of cell surface determinants in pathological processes.

A novel approach for the ultrastructural localization of surface sialic acids is presented. Membrane-bound sialyl residues are chemically modified in situ by the covalent attachment of biotinyl residues, the latter of which are subsequently localized by ferritin-conjugated avidin. In contrast to previous methods, which have been based on electrostatic interactions, the above method does not affect cell surface charge. Consequently, the macromolecular configuration of the labeled sialoglycoconjugates is preserved. The method has been found to be more accurate in the quantitative evaluation and the topographical localization of membrane-based sialic acids both in normal and pathologically induced surface modulations. Modulations in cell surface sialic acid content and/or distribution have been demonstrated in beta-thalassemia and transformed lymphoid cells, and the consequences of such alterations are discussed regarding destruction vs. escape from the immune surveillance system.