Release of Vitamin Binding Proteins from Granulocytes by Lithium: Vitamin B12 and Folate Binding Proteins

  • Victor Herbert
  • Neville Colman
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 127)


In 1968, Dr. Seymour Rosenblatt, a psychiatrist using lithium in the treatment of manic-depressive psychosis at the Mount Sinai Hospital in New York City called our attention to the fact that some of his patients receiving lithium appeared to have mild leukocytosis. Joint investigation of this phenomenon with him confirmed that such was the case, and we learned that this phenomenon had been observed as far back as 1955 (Bille and Plum).


Lithium Content Mount Sinai Hospital Calcium Ionophore A23187 Specific Granule Folate Binding Protein 
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  1. Baggiolini, M., deDuve, C., Masson, P.L., and Heremans, J.F., 1970, Association of lactoferrin with specific granules in rabbit heterophil leukocytes, J. Exp. Med. 131:559.PubMedCrossRefGoogle Scholar
  2. Bille, M. and Plum, C.M., 1955, Komplikationer ved lithium-behandling, Ugeskrift for Laeger 117:293.PubMedGoogle Scholar
  3. Bloomfield, J., Scott, J., Herbert, V., and Stebbins, R., 1973, Human serum unsaturated B12-binding capacity (UBBC) increases with increasing length of in vitro presence of granulocytes and certain anticoagulants especially those containing lithium, Fed. Proc. 32:892A.Google Scholar
  4. Boggs, D.R. and Winkelstein, A., 1975, “White Cell Manual”, 3rd Edition, F.A. Davis Company, Philadelphia.Google Scholar
  5. Broxrneyer, H.E., Smithyman, A., Eger, R.R., Myers, P.A., and de Sousa, M., 1978, Identification of lactoferrin as the granulocyte-derived inhibitor of colony-stimulating activity production,J. Exp. Med. 148:1052.CrossRefGoogle Scholar
  6. Buckley, R.M., Ventura, E.S., and MacGregor, R.R., 1978, Propranolol antagonizes the anti-inflammatory effect of alcohol and improves survival of infected intoxicated rabbits, J. Clin. Invest. 62(3):554.PubMedCrossRefGoogle Scholar
  7. Chikkappa, G., Corcino, J., Greenberg, M., and Herbert, V., 1969, Correlation of total blood leukocyte pools with B12 binding proteins, Blood 34:828.Google Scholar
  8. Chikkappa, G., Corcino, J., Greenberg, M., and Herbert, V., 1971, Correlation between various blood white cell pools and the serum B12-binding capacities, Blood 37:142.PubMedGoogle Scholar
  9. Colman, N. and Herbert, V., 1974a, Release of folate-binding protein (FBP) from granulocytes: Enhancement by lithium and elimination by fluoride; studies with normal, pregnant, chirrhotic, and uremic persons, Proc. 17th Ann. Mtg., Am. Soc. Hemat., Atlanta, Georgia, December 7–10.Google Scholar
  10. Colman, N. and Herbert, V., 1974b, Evidence for “granulocyte-related” and “liver-related” folate binders in human serum and renal glomerular filtration of folate binder, Clin. Res. 22:700A.Google Scholar
  11. Colman, N. and Herbert, V., 1979a, Kinetic and Chromatographic evidence for heterogeneity of high affinity folate binding proteins in serum, in: “Chemistry and Biology of Pteridines,” (R. Kisliuk and G. Brown, eds.) p. 525, EIsevier/North Holland, New York.Google Scholar
  12. Colman, N. and Herbert, V., 1979b, Studies using the calcium ionophore A23187 suggest localization of the human granulocyte folate binder in specific (secondary) granules, Clin. Res. 27:291A.Google Scholar
  13. Corcino, J., Krauss, S., Waxman, S., and Herbert, V., 1970, Release of vitamin B12-binding protein by human leukocytes in vitro, J. Clin. Invest. 49:2250.PubMedCrossRefGoogle Scholar
  14. Cutler, S.J. and Young, J.L., Jr., eds., 1975, Third National Cancer Survey: Incidence Data, DHEW Publication No. (NIH) 75-787, National Cancer Institute Monograph 4l.Google Scholar
  15. Dawson, E.B., Moore, T.D., and McGanity, W.J., 1970, The mathematical relationship of drinking water lithium and rainfall to mental hospital admission, Dis. Nerv. Syst. 21:811.Google Scholar
  16. Durfor, C.N. and Becker, E., 1964, Public water supplies of the hundred largest cities in the United States, 1962, in: “Geological Survey Water Supply Paper 1812,” U.S. Government Printing Office.Google Scholar
  17. Ford, J.E., 1974, Some observations on the possible nutritional significance of vitamin B12-and folate-binding proteins in milk, Brit. J. Nutr. 31:243.PubMedCrossRefGoogle Scholar
  18. Frenkel, E.P., 1975, Cancer in the Dallas — Fort Worth Metropolitan Area, in: “The Third National Cancer Survey Advanced Three Year Report (1969–1971 Incidence), ” DHEW Publcation No. (NIH) 75-641.Google Scholar
  19. Frenkel, E.P. and Herbert, V., 1974, Frequency of granulocytic leukemia in populations drinking high vs low lithium water, Clin. Res. 22:390A.Google Scholar
  20. Gelfand, E.W., Dosch, H.-M., Hastings, D., and Shore, A., 1979, Lithium: A modulator of cyclic AMP-dependent events in lymphocytes, Science 203:365.PubMedCrossRefGoogle Scholar
  21. Gibson, E.L., Herbert, V., and Robinson, W.A., 1974, Granulocyte colony stimulating activity and vitamin B12 binding proteins in human urine, Brit. J. Haemat. 28:193.CrossRefGoogle Scholar
  22. Gilbert, H.S., 1974, Proposal of a possible function for granulocyte vitamin B12 binding proteins in host defense against bacteria, Blood 44:926.Google Scholar
  23. Hammond, W.P. and Dale, D.C., 1979, Canine cyclic hematopoiesis (CH): Treatment with lithium, Clin. Res. 27:461A.Google Scholar
  24. Herbert, V., Bloomfield, J., Stebbins, R., and Scott, J., 1973, Use of fluoride to prevent erroneously high measurements of human serum unsat-urated B12-binding capacity (UBBC); evidence that granulocyte-derived binders (Transcobalamin I and III) (TC I and III) are a smaller component of normal circulating UBBC than previously believed, J. Clin. Invest. 52:39a.CrossRefGoogle Scholar
  25. Jacob, E. and Herbert, V., 1974, Lithium therapy for neutropenias, J. Clin. Invest. 53:359.Google Scholar
  26. Jim, R.T.S., 1979, Letter to the Editor, Blood 53:1031.PubMedGoogle Scholar
  27. Kane, S.P. and Peters, T.J., 1975, Analytical subcellular fractionation of human granulocytes with reference to the localization of vitamin B12 binding protein, Clin, Sci. Molec. Med. 49:171.Google Scholar
  28. Kurnick, J.E. and Robinson, W.A., 1971, Colony growth of human peripheral white blood cells in vitro, Blood 37:136.PubMedGoogle Scholar
  29. Perez, H.D., Kaplan, H., Shenkman, L., Borkowsky, W., and Goldstein, I., 1979, Reversal of an abnormality of polymophonuclear leukocyte chemotaxis with lithium, Clin, Res, 27:353A.Google Scholar
  30. Platman, S.R. and Fieve, R.R., 1968, Lithium carbonate and plasma cortisol response in the affective disorders, Arch. Gen, Psychiat. 18:591.CrossRefGoogle Scholar
  31. Robison, G.A., Butcher, R.W., and Sutherland, E.W., 1971, “Cyclic AMP,” Academic Press, New York.Google Scholar
  32. Scott, J.M., Bloomfield, F.J., Stebbins, R., and Herbert, V., 1974, Studies of derivation of transcobalamin III from granulocytes. Enhancement by lithium and elimination by fluoride of in vitro increments in vitamin B12-binding capacity, J. Clin. Invest, 53:228.PubMedCrossRefGoogle Scholar
  33. Shopsin, V., Friedmann, R., and Gershon, S., 1971, Lithium and leukocyto-sis, Clin, Pharmacol, Therap, 12:293Google Scholar
  34. Simon, J.D., Houck, W.D., and Albala, M.M., 1978, The effect of the calcium ionophore A23187 on the release of azurophilic and specific granule constituents of human granulocytes, Fed. Proc, 37:233.Google Scholar
  35. Spitznagel, J.K., Dalidorf, F.G., Leffell, M.S., Folds, J.D., Welsh, I.R., Cooney, M.H., and Martin, I.E., 1974, Character of azurophU and specific granules purified from human polymophonuclear leukocytes, Lab. Invest. 30:774.PubMedGoogle Scholar
  36. Stebbins, R. and Herbert, V., 1974, Studies of cyclic AMP effect on release of unsaturated vitamin B12 binding capacity from human blood cells, Proc, Soc, Exp, Biol. Med. 145:734.Google Scholar
  37. Tisman, G., 1974, Lithium carbonate protection against drug-induced leukopenia in lymphosarcoma patients, IRCS 2:1509.Google Scholar
  38. Tisman, G., Herbert, V., and Rosenblatt, S., 1972, Stimulation of granulo-cyte proliferation by lithium, Proc. 15th Ann. Mtg., Am. Soc. Hemat., Hollywood, Florida, December 3–6, 1972.Google Scholar
  39. Tisman, G., Herbert, V., and Rosenblatt, S., 1973, Evidence that lithium induces human granulocyte proliferation: Elevated serum B12 binding capacity in vivo and granulocyte colony proliferation in vitro, Brit. J, Haemat, 24:767.CrossRefGoogle Scholar
  40. Toohey, J.L., 1976, Letter to the Editor, Blood 47:166.PubMedGoogle Scholar
  41. Tosato, G., Whang-Peng, J., Levine, A.S., and Poplack, D.G., 1978, Acute lymphoblastic leukemia followed by chronic myelogenous leukemia, Blood 52:1033.PubMedGoogle Scholar
  42. Trieff, N.M., Frey, S.M., Rao, M.S., Bunce, H., III, and Herman, B., 1973, Analysis for lithium in Texas drinking waters, Texas Rpts. Biol. Med. 31:55.Google Scholar
  43. U.S. Bureau of Census, 1970, “Census of Population: 1970, General Population Characteristics, Final Report PC(1)-B1:U.S. Summary,” U.S. Government Printing Office.Google Scholar
  44. Voors, A.W., 1972, Drinking water lithium and mental hospital admission in North Carolina, N. Car. Med. J. 33:597.Google Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • Victor Herbert
    • 1
  • Neville Colman
    • 2
  1. 1.Hematology and Nutrition LaboratoryBronx Veterans Administration Medical CenterBronxUSA
  2. 2.Department of MedicineSUNY — Downstate Medical CenterBrooklynUSA

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