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Lactate dehydrogenase (LDH) isoenzymes and proliferative activity of lymphoid cells--an immunocytochemical study
L Pan1, P C Beverley, P G Isaacson
1Department of Histopathology, University College and Middlesex School of Medicine, London, England, UK.
Insights
Lactate dehydrogenase (LDH) isoenzymes, specifically H- and M-types, correlate with cell proliferation in human lymphocytes. Their expression patterns can help identify lymphocyte types and assess cell proliferation in normal and cancerous conditions.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Previous immunohistochemical studies suggested a link between lactate dehydrogenase (LDH) isoenzyme levels and cell proliferation.
- Further investigation is needed to understand the specific roles of H- and M-type LDH isoenzymes in lymphocyte activation and proliferation.
Purpose of the Study:
- To examine the expression of H- and M-type LDH isoenzymes in human resting and activated B and T lymphocytes using immunocytochemistry.
- To correlate LDH isoenzyme expression with cell cycle phases and proliferative activity.
- To evaluate the potential of LDH isoenzyme staining for identifying lymphocyte populations and assessing proliferation in neoplastic conditions.
Main Methods:
- Immunocytochemical analysis of H- and M-type LDH isoenzyme expression in human lymphocytes.
- Correlation of LDH expression with cell cycle status (S/G2/M phases).
- Examination of LDH expression in various lymphoid cell lines and leukemia samples.
Main Results:
- Resting T lymphocytes showed high H-type LDH and low M-type LDH; resting B lymphocytes showed low M-type LDH.
- During T cell activation, M-type LDH increased with cell cycle progression and decreased upon resting.
- Both H- and M-type LDH increased in activated B lymphocytes, correlating with cell cycle progression.
- Leukemia and lymphoid cell lines exhibited LDH patterns consistent with resting or activated lymphocytes.
Conclusions:
- LDH isoenzyme expression is significantly correlated with the proliferative activity of cells.
- Immunostaining for H- and M-type LDH can aid in identifying T and B lymphocytes.
- LDH isoenzyme analysis offers a valuable method for rapidly evaluating the proliferating fraction in normal and neoplastic human cell populations.
Abstract:
In a recent immunohistochemical study, we suggested that elevation of LDH isoenzymes is generally related to cell proliferation. To explore this relationship further, we have now examined the expression of H- and M-type LDH isoenzymes immunocytochemically in human resting and mitogen-activated B and T lymphocytes. In the resting state, T lymphocytes showed strong staining for H-type LDH but showed little or no staining for M-type LDH, while B lymphocytes showed only weak staining for M-type LDH. During activation of T cells, M-type LDH started to increase when cells entered the early stages of the cell cycle. The staining intensity increased to a maximum when the percentage of the T cells at the S/G2/M phases of the cell cycle reached its peak. M-type LDH expression declined when the activated T cells returned to their resting state. Staining for H-type LDH remained strong in T cells during activation. In B lymphocytes, both H- and M-type LDH isoenzymes increased concomitantly following activation and the staining intensity also correlated well with the percentage of the S/G2/M fraction. The expression of H- and M-type LDH was also determined in fresh leukaemia and a variety of lymphoid cell lines. It was noted that cells of chronic lymphocytic leukaemia (CLL) and pro-lymphocytic leukaemia (PLL), morphologically similar to normal lymphocytes, showed a LDH staining pattern resembling that of resting B lymphocytes, while lymphoblasts in T cell acute lymphoblastic leukaemia (T-ALL), high grade B cell lymphoma and Epstein-Barr virus (EBV) transformed cell lines showed a LDH staining pattern similar to that in activated T or B lymphocytes. Taken together, our results have demonstrated a significant correlation between expression of LDH and proliferative activity of cells. Immunostaining with the MoAbs to H- and M-type LDH can, therefore, provide a useful means not only for identification of T and B lymphocytes but also for rapid evaluation of the proliferating fraction of normal and neoplastic human cell populations.