Cell heterogeneity

In addition to IgE-dependent stimulation, mast cells may be activated for mediator release by non-immunological secretagogues such as neuropeptides, anaphylatoxins and xenobiotics, including morphine. 

Spectrum of mediators Histamine, PGD2, LTC4 Histamine only 

Kinetics of histamine release Slow, around 5 min Rapid, around 15 s 

Effect of immunological densensitization or removal of cell surface IgE Blockade of cell activation and mediator release No effect 

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Adt M, Marone G Human heart mast cells a definitive case of mast cell heterogeneity. Int Arch Allergy 29 Immunol 1995 106 386. 

Suslov, O.N., Kukekov, V.G., Ignatova, T.N., Steindler, D.A. (2002). Neural stem cell heterogeneity demonstrated by molecular phenotyping of clonal neurospheres. Proc Natl Acad Sc,. USA 99, 14506-11. 

Konemann, S., Schuck, A., Malath, J., Rupek, T., Horn, K., Baumann, M., Vormoor, J., Rube, C., and Willich, N. 2000. Cell heterogeneity and subpopulations in solid tumors characterized by simultaneous immunophenotyping and DNA content analysis. Cytometry 41 172-177. 

G. Ballardini, P. Groff, L. Badiali de Giorgi, D. Schuppan, and F. B. Bianchi, Ito cell heterogeneity desmin-negative Ito cells in normal rat liver, Hepatology 19 440-446 (1994). 

G. de Vries, A. Sherman and H.-R. Zhu Diffusively coupled bursters, effect of cell heterogeneity. Bull. Math. Biol. 1998, 60 1167-1200. 

Belloni, P. N. and Tressler, R. J. (1989/90). Microvascular endothehal cell heterogeneity interachons with leukocytes and tumor cells. Cancer Metastasis Rev. 8, 353-389. 

Poste, G., Tzeng, J., Doll, J., Greig, R., Rieman, D. and Zeldman, I. (1982), Evolution of tumor cell heterogeneity during progressive growth of individual lung metastases. Proc. Natl. Acad. Sci. USA 79, 6574-6578. 

Novikoff, A.B., Essner, E. Cell heterogeneity within the hepatic lohule of the rat staining reactions. J. Histochem. C tochem. 1959 7 240-244... 

Liver cell heterogeneity functions of non-parenchymal cells. Enzyme 1992 46 155-168... 

Mast cell heterogeneity in man. I. Histologic studies of the intestine. Int. Arch. Allergy Appl. Immunol. 76, 232-236. 

Goto T., Befits, D. Low, R, and Bienenstock, J. (1984). Mast cell heterogeneity and hyperplasia in bleomycin-induced... 

Lawrence, I.D., Warner, J.A., Cohan, V.L. etal. (1987). Purification and characterization of human skin mast cells. Evidence for human mast cell heterogeneity. J. Immunol. 139, 3062-3069. 

Shanahan F, Denburg JA, Fox J, Bienenstock J, Befus D Mast cell heterogeneity effects of neuroenteric peptides on histamine release. J Immunol 1985 135 1331-1337. 

None of the immunoreactive subpopulations of Golgi cells seem to correspond exclusively to one of the anatomical subtypes distinguished by Palay and Chan-Palay (1974). Similarly, Golgi cell heterogeneity due to differential expression of metabotropic glutamate receptors, does not correspond to any anatomical subdivision (see Section 3.3.2.). It remains to be elucidated to what extent the different immunocytochemical markers overlap. 

Wasscf M, Angaut P, Arsenio-Nunes L, Bourrat F, Sotelo C (1992c) Purkinje cell heterogeneity Its role in organizing the topography of the cerebellar cortex connections. In Llinas R, Sotelo C (Eds). The Cerebellum revisited. Springer-Verlag, New York. 

Castano JP, Kineman RJD, Frawley LS. Dynamic monitoring and quantification of gene expression in single, living cells A molecular basis for secretory cell heterogeneity. Mol Endocrinol 1996 10 599-605. 

Gene expression and cell heterogeneity in adult and developing smooth muscle cells... 

Zanellato AMC, Borrione AC, Giuriato L, Tonello M, Scannapieco G, Pauletto P, Sartore S (1990) Myosin isoforms and cell heterogeneity in vascular smooth muscle. I. Developing and adult bovine aorta, Dev Biol 141 431-446. 

To achieve the above goals, quantification of intracellular metabolite flow (or flux) is required. Presently, there are no efficient ways to quantify intracellular metabolite flux except for an isotope tracer technique using nuclear magnetic resonance (NMR) (Bonarius et al., 1997). However, this technique is expensive, laborious, and not suitable for industrial scale due to cell-to-cell heterogeneity. If a cell is dis-mpted in order to measure the concentration of different metabolites within cells to measure the flux, the internal environment such as the enzymatic control on metabolites is irreversibly lost and flux measurement becomes impossible. However, measurable rates such as substrate uptake rate and product secretion rates could be utilized to quantify internal metabolite flux. Besides, there are also certain conditions and constraints imposed while evaluating the flux across different pathways (Nielsen et al., 2003). 

Figure 21.5 presents the electropherograms generated from five cells. While some cells, such as cells 1 and 2, generate similar electropherograms, there is a fairly wide cell-to-cell heterogeneity in expression patterns. This pattern likely reflects the inherent heterogeneity in this complex primary cell type. 

Irani AA, Schwartz LB. Neutral proteases as indicators of human mast cell heterogeneity. In Schwartz LB, ed. Neutral Proteases of Mast Cells. Basel Karger, 1990 146. 

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