β-glucans are cell wall constituents of bacteria, yeast, fungi, and plants. They are not expressed in mammalian cells, but they are recognized by mammalian cells as pathogen-associated molecular patterns by pattern recognition receptors and thus act as biological response modifiers. This review summarizes data on the hematopoiesis-stimulating effects of β-glucans, as well as on their ability to enhance bone marrow recovery after an injury. β-glucans have been shown to support murine hematopoiesis suppressed by ionizing radiation or cytotoxic anti-cancer therapy. They also enhance stem cell homing and engraftment. Basically, two forms of β-glucan preparations have been investigated, namely particulate and soluble ones. β-glucans are generally well tolerated, the particulate forms showing a higher incidence of undesirable side effects. Taken together, the hematopoiesis-stimulating properties of β-glucans predetermine these biological response modifiers to ever increasing use in human medicinal practice.

Laboratory of Experimental Hematology Institute of Biophysics vvi Academy of Sciences of the Czech Republic Královopolská 135 CZ 61265 Brno Czech Republic

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Pilemer L., Ecker E.E. Anticomplementary factor in fresh yeast. J. Biol. Chem. 1941;137:139–142.

Di Carlo F.J., Fiore J.V. On the composition of zymosan. Science. 1958;127:756–757. PubMed

Riggi S.J., DiLuzio N.R. Identification of a reticuloendothelial stimulatory agent in zymosan. Am. J. Physiol. 1961;200:297–300. PubMed

Dunlap J., Minami E., Bhagwat A.A., Keister D.L., Stacey G. Nodule development induced by mutants of Bradyrhizobium japonicum defective in cyclic B-glucan synthesis. Mol. Plant Microbe Interact. 1996;9:546–555. doi: 10.1094/MPMI-9-0546. PubMed DOI

Magnani M., Castro-Gomez R.H., Aoki M.N., Gregorio E.P., Libos F., Watanabe M.A.E. Effects of carboxymethyl-glucan from Saccharomyces cerevisiae on the peripheral blood cells of patients with advanced prostate cancer. Exp. Ther. Med. 2010;5:859–862.

Ohno N., Miura N.N., Nakajima M., Yadomae T. Antitumor 1,3-beta-glucan from cultured fruit body of Sparassis crispa. Biol. Pharm. Bull. 2000;23:866–872. doi: 10.1248/bpb.23.866. PubMed DOI

Chang R. Bioactive polysaccharides from traditional Chinese medicine herbs as anticancer adjuvants. J. Altern. Complement. Med. 2002;8:559–565. doi: 10.1089/107555302320825066. PubMed DOI

Marklinder I., Johansson L., Haglund A., NagelHeld B., Seibel W. Effects of flour from different barley varieties on barley sour dough bread. Food Qual. Preference. 1996;7:275–284. doi: 10.1016/S0950-3293(96)00033-X. DOI

Lin H., De Stanchina E., Zhou X.K., She Y., Hoang D., Cheung S.W.Y., Cassileth B., Cunningham-Rundles S. Maitake beta-glucan enhances umbilical cord blood stem cell transplantation in the DOD/SCID mouse. Exp. Biol. Med. 2009;234:342–353. doi: 10.3181/0807-RM-226. PubMed DOI PMC

DiLuzio N.R. Immunopharmacology of glucan: A broad spectrum enhancer of host defense mechanisms. Trends Pharmacol. Sci. 1983;4:344–347. doi: 10.1016/0165-6147(83)90434-0. DOI

DiLuzio N.R. Update on the immunomodulating activities of glucan. Springer Semin. Immunopathol. 1985;8:387–400. doi: 10.1007/BF01857392. PubMed DOI

Kokoshis P.L., Williams D.L., Cook J.A., DiLuzio N.R. Increased resistance to Staphylococcus-aureus infection and enhancement in serum lysozyme activity by glucan. Science. 1987;199:1340–1342. PubMed

DiLuzio N.R., Williams D.L. Protective effects of glucan against systemic Staphylococcus aureus septicemia in normal and leukemic mice. Infect. Immun. 1978;20:804–810. PubMed PMC

Williams D.L., DiLuzio N.R. Glucan-induced modification of murine viral-hepatitis. Science. 1980;208:67–69. PubMed

Williams D.L., Cook J.A., Hoffmann E.O., DiLuzio N.R. Protective effects of glucan in experimentally induced candidiasis. J. Reticuloendothel. Soc. 1978;23:479–490. PubMed

Browder I.W., Williams D.L., Kitahama A., DiLuzio N.R. Modification of postoperative C-albicans sepsis by glucan immunostimulation. Int. J. Immunopharmacol. 1984;6:19–26. doi: 10.1016/0192-0561(84)90030-4. PubMed DOI

Williams D.L., Mueller A., Browder W. Glucan-based macrophage stimulators: A review of their anti-infective potential. Clin. Immunother. 1996;9:392–399.

Novelli E.M., Ramirez M., Civin C.I. Biology of CD34+CD38− cells in lymphohematopoiesis. Leuk. Lymphoma. 1998;31:285–293. PubMed

Grande T., Varas F., Bueren J.A. Residual damage of lymphohematopoietic repopulating cells after irradiation of mice at different stages of development. Exp. Hematol. 2000;28:87–95. PubMed

Burgaleta C., Golde D.W. Effect of glucan on granulopoiesis and macrophage genesis in mice. Cancer Res. 1977;37:1739–1742. PubMed

Niskanen E.O., Burgaleta C., Cline M.J., Golde D.W. Effect of glucan, a macrophage activator, on murine hemopoietic cell proliferation in diffusion chambers in mice. Cancer Res. 1978;38:1406–1409. PubMed

Patchen M.L., Lotzová E. Modulation of murine hemopoiesis by glucan. Exp. Hematol. 1980;8:409–422. PubMed

Patchen M.L., MacVittie T.J. Dose-dependent responses of murine pluripotent stem cells and myeloid and erythroid progenitor cells following administration of the immunomodulating agent glucan. Immunopharmacology. 1983;5:303–313. doi: 10.1016/0162-3109(83)90046-2. PubMed DOI

Patchen M.L., MacVittie T.J. Temporal response of murine pluripotent stem cells and myeloid and erythroid progenitor cells to low-dose glucan treatment. Acta Haematol. 1983;70:281–288. doi: 10.1159/000206753. PubMed DOI

Patchen M.L., MacVittie T.J. Hemopoietic effects of intravenous soluble glucan administration. J. Immunopharmacol. 1986;8:407–425. doi: 10.3109/08923978609026497. PubMed DOI

Hashimoto K., Suzuki I., Ohsawa M., Oikawa S., Yadomae T. Enhancement of hematopoietic response of mice by intraperitoneal administration of a β-glucan, SSG, obtained from Sclerotinia sclerotiorum. J. Pharmacobio-Dyn. 1990;13:512–517. doi: 10.1248/bpb1978.13.512. PubMed DOI

Pospíšil M., Jarý J., Netíková J., Marek M. Glucan-induced enhancement of hemopoietic recovery in gamma-irradiated mice. Experientia. 1982;38:1232–1234. doi: 10.1007/BF01959759. PubMed DOI

Pospíšil M., Šandula J., Pipalová I., Hofer M., Viklická Š. Hemopoiesis stimulating and radioprotective effects of carboxymethylglucan. Physiol. Res. 1991;40:377–380. PubMed

Hofer M., Pospíšil M., Viklická Š., Pipalová I., Holá J., Netíková J., Šandula J. Effects of postirradiation carboxymethylglucan administration in mice. Int. J. Immunopharmacol. 1995;17:167–174. doi: 10.1016/0192-0561(95)00002-J. PubMed DOI

Hofer M., Pospíšil M., Pipalová I., Holá J., Šandula J. Haemopoiesis-enhancing effects of repeatedly administered carboxymethylglucan in mice exposed to fractionated irradiation. Folia Biol. (Praha) 1995;41:249–256. PubMed

Hofer M., Pospíšil M. Glucan as stimulator of hematopoiesis in normal and gamma-irradiated mice. A survey of the authors’ results. Int. J. Immunopharmacol. 1997;19:607–609. doi: 10.1016/S0192-0561(97)00057-X. PubMed DOI

Patchen M.L., MacVittie T.J. In: Macrophages and Natural Killer Cells. Norman J.J., Sorkin E., editors. Plenum Publishing Corporation; New York, NY, USA: 1982. pp. 267–272.

Patchen M.L., MacVittie T.J. Stimulated hemopoiesis and enhanced survival following glucan treatment in sublethally and lethally irradiated mice. Int. J. Immunopharmacol. 1985;7:923–932. doi: 10.1016/0192-0561(85)90056-6. PubMed DOI

Patchen M.L., MacVittie T.J., Wathen L.M. Effects of pre- and post-irradiation glucan treatment on pluripotent stem cells, granulocyte, macrophage and erythroid progenitor cells, and hemopoietic stromal cells. Experientia. 1984;40:1240–1244. doi: 10.1007/BF01946654. PubMed DOI

Patchen M.L., MacVittie T.J., Brook I. Glucan-induced hemopoietic and immune stimulation: Therapeutic effects in sublethally and lethally irradiated mice. Meth. Find. Exp. Clin. Pharmacol. 1986;8:151–155. PubMed

Patchen M.L., D’Alesandro M.M., Brook I., Blakely W.F., MacVittie T.J. Glucan: Mechanisms involved in its "radioprotective" effect. J. Leukoc. Biol. 1987;42:95–105. PubMed

Patchen M.L., DiLuzio N.R., Jacques P., MacVittie T.J. Soluble polyglycans enhance recovery from cobalt-60-induced hemopoietic injury. J. Biol. Response Mod. 1984;3:627–633. PubMed

Patchen M.L., Brook I., Elliott T.B., Jackson W.E. Adverse effects of pefloxacin in irradiated C3H/HeN mice: Correction with glucan therapy. Antimicrob. Agents Chemother. 1993;37:1882–1889. doi: 10.1128/AAC.37.9.1882. PubMed DOI PMC

Pospíšil M., Netíková J., Pipalová I., Jarý J. Combined radioprotection by preirradiation peroral cystamine and postirradiation glucan administration. Folia Biol. (Praha) 1991;37:117–124. PubMed

Patchen M.L., D’Alesandro M.M., Chirigos M.A., Weiss J.F. Radioprotection by biological response modifiers alone and in combination with WR-2721. Pharmacol. Ther. 1988;39:247–254. doi: 10.1016/0163-7258(88)90068-X. PubMed DOI

Patchen M.L., MacVittie T.J., Weiss J.F. Combined modality radioprotection: The use of glucan and selenium with WR-2721. Int. J. Radiat. Oncol. Biol. Phys. 1990;18:1069–1075. doi: 10.1016/0360-3016(90)90442-M. PubMed DOI

Patchen M.L., MacVittie T.J., Solberg B.D., Souza L.M. Survival enhancement and hemopoietic regeneration following radiation exposure: Therapeutic approach using glucan and granulocyte colony-stimulating factor. Exp. Hematol. 1990;18:1042–1048. PubMed

Pospíšil M., Hofer M., Pipalová I., Viklická Š., Netíková J., Šandula J. Enhancement of hematopoietic recovery in gamma-irradiated mice by the joint use of diclofenac, an inhibitor of prostaglandin production, and glucan, a macrophage activator. Exp. Hematol. 1992;20:891–895. PubMed

Hofer M., Pospíšil M., Viklická Š., Vacek A., Pipalová I., Bartoníčková A. Hematopoietic recovery in repeatedly irradiated mice can be enhanced by a repeatedly administered combination of diclofenac and glucan. J. Leukoc. Biol. 1993;53:185–189. PubMed

Líšková A., Wagnerová J., Červeňáková L., Krištofová A., Ferenčík M. The effect of soluble glucan derivates on spleen colony-forming units in sublethally irradiated mice. Folia Microbiol. 1990;35:353–362. doi: 10.1007/BF02821287. PubMed DOI

Cramer D.E., Allendorf D.J., Baran J.T., Hansen R., Marroquin J., Li B., Ratajczak J., Ratajczak M.Z., Yan J. β-Glucan enhances complement-mediated hematopoietic recovery after bone marrow injury. Blood. 2006;107:835–840. doi: 10.1182/blood-2005-07-2705. PubMed DOI PMC

Wagnerová J., Líšková A., Navarová J., Krištofová A., Trnovec T., Ferenčík M. The effects of two glucan carboxymethylderivatives with various substitution degress on cyclophosphamide immunosuppression in mice. Immunopharmacol. Immunotoxicol. 1993;15:227–242. doi: 10.3109/08923979309025996. PubMed DOI

Patchen M.L., Vaudrain T., Correira H., Martin T., Reese D. In vitro and in vivo hematopoietic activities of Betafectin® PGG-glucan. Exp. Hematol. 1998;13:1247–1254. PubMed

Lin H., She Y.-H., Cassileth B.R., Sirotnak F., Cunningham-Rundles S. Maitake beta-glucan MD-fraction enhances bone marrow colony formation and reduces doxorubicin toxicity in vitro. Int. Immunopharmacol. 2004;4:91–99. doi: 10.1016/j.intimp.2003.10.012. PubMed DOI

Ito K., Masuda Y., Yamasaki Y., Yokota Y., Nanba H. Maitake beta-glucan enhances granulopoiesis and mobilization of granulocytes by increasing G-CSF production and modulating CXCR4/SDF-1 expression. Int. Immunopharmacol. 2009;9:1189–1196. doi: 10.1016/j.intimp.2009.06.007. PubMed DOI

Harnack U., Eckert K., Fichtner I., Pecher G. Comparison of the effect of orally administered soluble beta-(1,3),(1,6)-D-glucan and of G-CSF on the recovery of murine hematopoiesis. In Vivo. 2010;24:59–63. PubMed

Lin H., Cheung S.W.Y., Nesin M., Cassileth B.R., Cunningham-Rundles S. Enhancement of umbilical cord blood cell hematopoiesis by maitake beta-glucan is mediated by granulocyte colony-stimulating factor production. Clin. Vaccine Immunol. 2007;14:21–27. doi: 10.1128/CVI.00284-06. PubMed DOI PMC

Patchen M.L., Liang J., Vaudrain T., Martin T., Melican D., Zhong S., Stewart M., Quesenberry P.J. Mobilization of peripheral blood progenitor cells by betafectin® PGG-glucan alone and in combination with granulocyte colony-stimulating factor. Stem Cells. 1998;16:208–217. doi: 10.1002/stem.160208. PubMed DOI

Torello C.O., de Souza Queiroz J., OLiveira S.C., Queiroz M.L.S. Immunohematopoietic modulation by oral β-1,3-glucan in mice infected with Listeria monocytogenes. Int. Immunopharmacol. 2010;10:1573–1579. doi: 10.1016/j.intimp.2010.09.009. PubMed DOI

Sherwood E.R., Williams D.L., McNamee R.B., Jones E.L., Browder I.W., Di Luzio N.R. Enhancement of interleukin-1 and interleukin-2 production by soluble glucan. Int. J. Immunopharmacol. 1987;9:261–267. doi: 10.1016/0192-0561(87)90049-X. PubMed DOI

Abel G., Czop J.K. Stimulation of human monocyte β-glucan receptors by glucan particles induces production of TNF-α and IL-1β. Int. J. Immunopharmacol. 1992;14:1363–1373. doi: 10.1016/0192-0561(92)90007-8. PubMed DOI

Dorie M.J., Allison A.C., Zaghloul M.S., Kallman R.F. Interleukin 1 protects against the lethal effects of irradiation of mice but has no effect on tumors in the same animals. Proc. Soc. Exp. Biol. Med. 1989;191:23–29. PubMed

Turnbull J.L., Patchen M.L., Scadden D.T. The polysaccharide, PGG-glucan, enhances human myelopoiesis by direct action independent of and additive to early-acting cytokines. Acta Haematol. 1999;102:66–71. doi: 10.1159/000040972. PubMed DOI

Deimann W., Fahimi H.D. Hepatic granulomas induced by glucan. An ultrastructural and peroxidase-cytochemical study. Lab. Invest. 1980;43:172–181. PubMed

Kimura A., Sherwood R.L., Goldstein E. Glucan alteration of pulmonary antibacterial defense. J. Reticuloendothel. Soc. 1983;34:1–11. PubMed

Pospíšil M., Tkadleček L., Netíková J., Pipalová I., Viklická Š., Kozubík A., Vácha J., Jarý J. Interstrain differences in the responsivenss of mice to glucan with respect to hematological effects and manifestations of late damage. Exp. Pathol. 1988;33:27–36. doi: 10.1016/S0232-1513(88)80052-5. PubMed DOI

Bowers G.J., Patchen M.L., MacVittie T.J., Hirsch E.F., Fink M.P. A comparative evaluation of particulate and soluble glucan in an endotoxin model. Int. J. Immunopharmacol. 1986;8:313–321. doi: 10.1016/0192-0561(86)90113-X. PubMed DOI

Di Luzio N.R., Williams D.L., McNamee R.B., Edwards B.F., Kitahama A. Comparative tumor-inhibitory and anti-bacterial activity of soluble and particulate glucan. Int. J. Cancer. 1979;24:773–779. doi: 10.1002/ijc.2910240613. PubMed DOI

Baker W.H., Nold J.B., Patchen M.L., Jackson W.E. Histopathologic effects of soluble glucan and WR-2721, independently and combined in C3H/HeN mice. Proc. Soc. Exp. Biol. Med. 1992;201:180–191. PubMed

Vácha J., Znojil V., Pospíšil M., Holá J., Pipalová I. Microcytic anemia and changes in ferrokinetics as late after-effects of glucan administration in murine hepatitis virus-infected C57BL/10ScSnPh mice. Int. J. Immunopharmacol. 1994;16:51–60. doi: 10.1016/0192-0561(94)90118-X. PubMed DOI

Pospíšil M., Vacek A., Hofer M., Viklická Š., Pipalová I., Šandula J. Hyporesponsiveness of murine myeloid progenitor cells to glucan following its repeated administration. Folia Biol. (Praha) 1993;178-187 PubMed

Williams D.L., Sherwood E.R., Browder I.W., McNamee R.B., Jones E.L., DiLuzio N.R. Pre-clinical safety evaluation of soluble glucan. Int. J. Immunopharmacol. 1988;10:405–414. doi: 10.1016/0192-0561(88)90127-0. PubMed DOI

Browder W., Williams D., Pretus H., Oliveiro G., Enrichens F., Mao P., Franchello A. Beneficial effect of enhanced macrophage function in the trauma patient. Ann. Surg. 1990;211:605–613. PubMed PMC

Spruijt N.E., Visser T., Leenen L.P.H. A systematic review of randomized controlled trials exploring the effect of immunomodulative interventions on infection, organ failure, and mortality in trauma patients. Crit. Care. 2010;14:R150. doi: 10.1186/cc9218. PubMed DOI PMC

Babineau T.J., Marcello P., Swails W., Kenler A., Bistrian B., Forse R.A. Randomized phase I/II trial of a macrophage-specific immunomodulator (PGG-glucan) in high-risk surgical patients. Ann. Surg. 1994;220:601–609. doi: 10.1097/00000658-199411000-00002. PubMed DOI PMC

Weitberg A.B. A phase I/II trial of beta-(1,3)/(1,6) D-glucan in the treatment of patients with advanced malignancies receiving chemotherapy. J. Exp. Clin. Cancer Res. 2008;27:40. doi: 10.1186/1756-9966-27-40. PubMed DOI PMC

Hong F., Yan J., Baran J.T., Allendorf D.J., Hansen R.D., Ostroff R., Xing P.X., Cheung N.-K.V., Ross G.D. Mechanisms by which orally administered β-1,3-glucans enhance the tumoricidal activity of antitumor monoclonal antibodies in murine tumor models. J. Immunol. 2004;173:797–806. PubMed

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