Phytohemagglutinin stimulation

Fig. 11.2. The gradual increase in expression of interleukin-2 receptors on the surface of lymphocytes after phytohemagglutinin stimulation.

Reduced incorporation of thymidine into phytohemagglutinin-stimulated lymphocytes, reduced bactericidal activity... 

Bone resorption occurs when osteoclasts are activated to produce proteases and collagenase by parathyroid hormone or by osteoclast activating factor (derived from phytohemagglutinin stimulated lymphocytes). Although trasylol and soybean trypsin Inhibitor do not affect bone resorption, a specific cartilage-derived antl-collagenase seems to be active. 

Kaczmarek, L., Calabretta, B., and Baserga, R. (1985) Expression of Cell-Cycle-Dependent Genes in Phytohemagglutinin-Stimulated Human Lymphocytes, Proc. Natl. Acad. Sci. USA 2,5375-5379. 

Yoshimura, T., Robinson, E. A., Tanaka, S., Appella, E., and Leonard, E. J. (1989b). Purification and amino acid analysis of two human monocyte chemoattractants produced by phytohemagglutinin-stimulated human blood mononuclear leukocytes. J. Immunol. 142, 1956-1962. 

Because of the apparent correlation between alkylation and derepression of DNA, Pogo, Allfrey, and Mirsky [71, 72] studied the incorporation of [ C]ace-tateinto histone [ " C]uridine into RNA [ C]thymi-dine into DNA and [ " C]alanine into protein of phy-tohemagglutinin-stimulated lymphocytes. Acetylation preceded RNA synthesis, which itself preceded the synthesis of some of the protein. DNA and histone synthesis occurred late in the sequence of events that followed phytohemagglutinin stimulation. The fact that histone acetylation preceded nuclear RNA synthesis was considered evidence that acetylation signals derepression of DNA. 

Inasmuch as TTP, one of the four triphosphate nucleotides needed for DNA synthesis, is formed through the methylation of UMP to TMP which is then further phosphorylated, one may expect that a reduction in methyl transfer would reduce the levels of TTP and thereby cause interference with DNA synthesis and maturation of the red cell. Yet, the pools of TTP in lymphocytes were normal in untreated patients deficient in vitamin Bi2- In contrast, in patients treated with methotrexate a marked drop in the TTP pool is found [166]. A drop in thymidylate synthetase activity in phytohemagglutinin stimulated lymphocytes of patients with pernicious anemia has been described. 

In discussing the pathogenesis of vitamin B12 deficiency we have mentioned that a defect in the methyla-tion of UMP to TMP could explain the block of DNA synthesis and the lack of maturation of the red cell. It could be expected that patients receiving methotrexate which decreases the level of 5,10-methylenetetra-hydrofolate, a coenzyme indispensable for the synthesis of TMP, would present similar symptoms. Phytohemagglutinin stimulated lymphocytes of patients treated with methotrexate have very low pools of TTP. Whether this is the only biochemical distortion leading to the lack of maturation of the red cells remains to be seen. 

F. Quagliata, D. Faig, M. Conly, and R. Silber, Studies on the lymphocyte 5 -nucleotidase in chronic lymphocytic leukemia, infectious mononucleosis, normal subpopulations, and phytohemagglutinin-stimulated cells. Cancer Res.. 34 3197 (1974). 

R.J. Hayman and M.B. Van Der Weyden. Phytohemagglutinin stimulated normal human peripheral blood lymphocytes in folate depleted medium an in vitro model for megaloblastic hemopoiesis. Blood 55 803, 1980. 

B. Munch-Petersen, G. Tyrsted and B. Dupont. The deoxy-ribonucleoside-5 -triphosphate (dATP and dTTP pool) in phytohemagglutinin stimulated and non stimulated human l3nnphocytes. 

Skinnider, L. F., Giesbrecht, K. (1981). Inhibition of phorbol myristate acetate and phytohemagglutinin stimulation of human lymphocytes ty 13-cis-retinoic acid and ethyletri-noate. Experientia 37 1345-1346. 

Although the exact DNA replicase of animal cells has not been conclusively identified, it is believed that DNA polymerase I (or a) is most likely the DNA replicase. In phytohemagglutinin-stimulated human lymphocytes, polymerase I activity increased with DNA synthesis (Ber-tazzoni et al., 1976). In HeLa cells, DNA polymerase I increased tenfold during the Gi period and decreased after the S period (Chiu and Baril, 1975). In mice, polymerase I increased during liver regeneration (Hecht, 1975). 

Schumm, D. E., Morris, H. P., and Webb, T. E., 1974, Early biochemical changes in phytohemagglutinin-stimulated peripheral blood lymphocytes from normal and tumor-bearing rats, Eur. J. Cancer 10 107. 

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