Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1985 Apr;82(8):2508–2512. doi: 10.1073/pnas.82.8.2508

Bone marrow engraftment efficiency is enhanced by competitive inhibition of the hepatic asialoglycoprotein receptor.

W E Samlowski, R A Daynes
PMCID: PMC397588  PMID: 3887405

Abstract

The efficiency of pluripotent stem cell engraftment following bone marrow transplantation is predicated upon many poorly understood factors. These include the processes by which intravenously injected stem cells circulate and localize in microenvironments that contain the stromal elements necessary to facilitate their continued proliferation. We have recently established that lymphoid cells that bind the lectin peanut agglutinin are subject to prolonged sequestration following their interaction with the hepatic asialoglycoprotein receptor. Since bone marrow stem cells are also known to bind peanut agglutinin, we hypothesized that the physiologic function of the asialoglycoprotein receptor might significantly impair their ability to localize in anatomic sites where they are able to proliferate. Competitive inhibition with asialoglycoproteins was employed to establish a temporary receptor blockade during the initial 3-4 hr after transplantation. This procedure resulted in a 5- to 10-fold increase in splenic hematopoietic colony formation. Our findings suggest that inhibition of the liver asialoglycoprotein receptor during murine bone marrow transplantation results in more efficient stem cell localization to hematopoietic-inducing microenvironments. This enhancement in engraftment efficiency was paralleled by a more rapid recovery of peripheral blood leukocyte and platelet counts, an increase in megakaryocytic colony formation, as well as increased recipient survival. Techniques designed to inhibit the liver sequestration of bone marrow stem cells may have direct applicability to human bone marrow transplantation procedures.

Full text

PDF
2508

Images in this article

2510Image
on p.2510
2510Image
on p.2510
2510Image
on p.2510
2511Image
on p.2511

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AMINOFF D. Methods for the quantitative estimation of N-acetylneuraminic acid and their application to hydrolysates of sialomucoids. Biochem J. 1961 Nov;81:384–392. doi: 10.1042/bj0810384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ashwell G., Harford J. Carbohydrate-specific receptors of the liver. Annu Rev Biochem. 1982;51:531–554. doi: 10.1146/annurev.bi.51.070182.002531. [DOI] [PubMed] [Google Scholar]
  3. Baenziger J. U., Maynard Y. Human hepatic lectin. Physiochemical properties and specificity. J Biol Chem. 1980 May 25;255(10):4607–4613. [PubMed] [Google Scholar]
  4. Barker J. E., Keenan M. A., Raphals L. Development of the mouse hematopoietic system. II. Estimation of spleen and liver "stem" cell number. J Cell Physiol. 1969 Aug;74(1):51–56. doi: 10.1002/jcp.1040740107. [DOI] [PubMed] [Google Scholar]
  5. Galili U., Galili N., Or R., Polliack A. Analysis of the peanut agglutinin-binding site as a differentiation marker of normal and malignant human lymphoid cells. Clin Exp Immunol. 1981 Feb;43(2):311–318. [PMC free article] [PubMed] [Google Scholar]
  6. Lambertsen R. H., Weiss L. A model of intramedullary hematopoietic microenvironments based on stereologic study of the distribution of endocloned marrow colonies. Blood. 1984 Feb;63(2):287–297. [PubMed] [Google Scholar]
  7. London J., Berrih S., Bach J. F. Peanut agglutinin. I. A new tool for studying T lymphocyte subpopulations. J Immunol. 1978 Aug;121(2):438–443. [PubMed] [Google Scholar]
  8. Regoeczi E., Chindemi P. A., Hatton M. W., Berry L. R. Galactose-specific elimination of human asialotransferrin by the bone marrow in the rabbit. Arch Biochem Biophys. 1980 Nov;205(1):76–84. doi: 10.1016/0003-9861(80)90085-5. [DOI] [PubMed] [Google Scholar]
  9. Reinherz E. L., Geha R., Rappeport J. M., Wilson M., Penta A. C., Hussey R. E., Fitzgerald K. A., Daley J. F., Levine H., Rosen F. S. Reconstitution after transplantation with T-lymphocyte-depleted HLA haplotype-mismatched bone marrow for severe combined immunodeficiency. Proc Natl Acad Sci U S A. 1982 Oct;79(19):6047–6051. doi: 10.1073/pnas.79.19.6047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Reisner Y., Itzicovitch L., Meshorer A., Sharon N. Hemopoietic stem cell transplantation using mouse bone marrow and spleen cells fractionated by lectins. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2933–2936. doi: 10.1073/pnas.75.6.2933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Reisner Y., Kapoor N., Kirkpatrick D., Pollack M. S., Dupont B., Good R. A., O'Reilly R. J. Transplantation for acute leukaemia with HLA-A and B nonidentical parental marrow cells fractionated with soybean agglutinin and sheep red blood cells. Lancet. 1981 Aug 15;2(8242):327–331. doi: 10.1016/s0140-6736(81)90647-4. [DOI] [PubMed] [Google Scholar]
  12. Samlowski W. E., Spangrude G. J., Daynes R. A. Studies on the liver sequestration of lymphocytes bearing membrane-associated galactose-terminal glycoconjugates: reversal with agents that effectively compete for the asialoglycoprotein receptor. Cell Immunol. 1984 Oct 15;88(2):309–322. doi: 10.1016/0008-8749(84)90164-3. [DOI] [PubMed] [Google Scholar]
  13. Spangrude G. J., Bernhard E. J., Ajioka R. S., Daynes R. A. Alterations in lymphocyte homing patterns within mice exposed to ultraviolet radiation. J Immunol. 1983 Jun;130(6):2974–2981. [PubMed] [Google Scholar]
  14. Spruce W. E., McMillan R., Miller W., Fox R., Carson D., Schwartz D. B., Hartman G. A., Renshaw L. W., Beutler E. Transplantation of T-lymphocyte-depleted bone marrow between HLA-mismatched individuals. Transplantation. 1983 Oct;36(4):369–372. doi: 10.1097/00007890-198310000-00004. [DOI] [PubMed] [Google Scholar]
  15. TILL J. E., MCCULLOCH E. A., SIMINOVITCH L. A STOCHASTIC MODEL OF STEM CELL PROLIFERATION, BASED ON THE GROWTH OF SPLEEN COLONY-FORMING CELLS. Proc Natl Acad Sci U S A. 1964 Jan;51:29–36. doi: 10.1073/pnas.51.1.29. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. TILL J. E., McCULLOCH E. A. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res. 1961 Feb;14:213–222. [PubMed] [Google Scholar]
  17. Tavassoli M., Friedenstein A. Hemopoietic stromal microenvironment. Am J Hematol. 1983 Sep;15(2):195–203. doi: 10.1002/ajh.2830150211. [DOI] [PubMed] [Google Scholar]
  18. Thierfelder S., Hoffmann-Fezer G., Rodt H., Doxiadis I., Eulitz M., Kummer U. Antilymphocytic antibodies and marrow transplantation. VI. Absence of immunosuppression in vivo after injection of monoclonal antibodies blocking graft-versus-host reactions and humoral antibody formation in vitro. Transplantation. 1983 Mar;35(3):249–254. [PubMed] [Google Scholar]
  19. Trentin J. J. Determination of bone marrow stem cell differentiation by stromal hemopoietic inductive microenvironments (HIM). Am J Pathol. 1971 Dec;65(3):621–628. [PMC free article] [PubMed] [Google Scholar]
  20. Winston D. J., Gale R. P., Meyer D. V., Young L. S. Infectious complications of human bone marrow transplantation. Medicine (Baltimore) 1979 Jan;58(1):1–31. doi: 10.1097/00005792-197901000-00001. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES