Lactate dehydrogenase enhances immunoglobulin production by human hybridoma and human peripheral blood lymphocytes

Abstract

Lactate dehydrogenase (LDH) derived from rabbit muscle enhanced IgM production by human-human hybridoma HB4C5 cells 12.4-fold at 320 g/ml under serum-free conditions. LDHs from pig muscle and pig heart also accelerated IgM production 8.4-and 6.4-fold, respectively. The immunoglobulin production stimulating activity of LDH was not accompanied by activation of cell proliferation. LDH from rabbit muscle facilitated IgM and IgG production by human peripheral blood lymphocytes. This means LDH stimulates immunoglobulin production not only by the specified hybridoma cell line, but also by unspecified immunoglobulin producers. LDH from rabbit muscle enhanced IgM production of transcription-suppressed HB4C5 cells treated with actinomycin D. The immunoglobulin production-stimulating factors (IPSFs) effect of LDH was slightly weakened by sodium fluoride (translation inhibitor) treatment of HB4C5. Moreover, the amount of intracellular IgM of monensin-treated HB4C5 cells was obviously enhanced by LDH. This result means that the IPSF effect of LDH is irrelevant to the post-translation activity of target cells. It is expected from these findings that LDH from rabbit muscle accelerates the translation step to enhance immunoglobulin productivity. The immunoglobulin production-stimulating activity of LDH was inhibited by colchicine, endocytosis inhibitor. This fact suggests that it is necessary for LDH to be taken by target cells to act as an IPSF.

Immunostimulatoryin Vitroandin VivoEffects of a Water-Soluble Extract from Kale

“…It is therefore suggested that the kale extract affected the HB4C5 cells in the post-transcriptional stages such as the translational and/or protein-secreting processes to enhance the IgM production. These results are consistent with other IPSFs; [16][17][18][19] for example, lysozyme is one of the strong IPSFs and accelerated IgM production in both Act D-treated and non-treated HB4C5 cells. 20) The stimulatory effect of the kale extract on the Act Dtreated HB4C5 cells was lower than that on the intact HB4C5 cells.…”

Enhancement of antibody production by the addition of Coenzyme-Q10

“…Over the past decade, various approaches such as genetic engineering, clone selection, medium optimization, and reactor engineering have dramatically improved production (Takenouchi and Sugahara 2003). The addition of an enhancer has also proven effective.…”

Activation of J774.1 murine macrophages by lactate dehydrogenase

“…It was also confirmed that the immunomodulatory activity of LDH does not depend on its enzyme activity (Sugahara et al 1998). Thus, it was thinkable that the protein structure of LDH stimulates lymphocytes (Takenouchi and Sugahara 2002). LDH ubiquitously and abundantly exists in most of the tissues in humans, especially in kidney, heart, skeletal muscle, pancreas, spleen, liver, and lung.…”

“…LDH is known to play a crucial role in maintaining aerobic metabolism by converting lactate to pyruvate in muscle and to exist ubiquitously not only in fish but also in all vertebrate organisms. We previously evaluated that the immunostimulatory effect of LDH is a novel function, which is independent of the enzymatic activity of the enzyme (Sugahara et al 1998;Takenouchi and Sugahara 2002). In addition, oral administration of LDH increased the IgA level in serum from BALB/c mice (Daifuku et al 2012b).…”