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. 1995 Oct 10;92(21):9647–9651. doi: 10.1073/pnas.92.21.9647

The VLA4/VCAM-1 adhesion pathway defines contrasting mechanisms of lodgement of transplanted murine hemopoietic progenitors between bone marrow and spleen.

T Papayannopoulou 1, C Craddock 1, B Nakamoto 1, G V Priestley 1, N S Wolf 1
PMCID: PMC40859  PMID: 7568190

Abstract

Selective lodgement or homing of transplanted hemopoietic stem cells in the recipient's bone marrow (BM) is a critical step in the establishment of long-term hemopoiesis after BM transplantation. However, despite its biologic and clinical significance, little is understood about the process of homing. In the present study, we have concentrated on the initial stages of homing and explored the functional role in vivo of some of the adhesion pathways previously found to mediate in vitro adhesion of hemopoietic cells to cultured BM stroma. We have found that homing of murine hemopoietic progenitors of the BM of lethally irradiated recipients at 3 h after transplant was significantly reduced after pretreatment of the donor cells with an antibody to the integrin very late antigen 4 (VLA4). This inhibition of marrow homing was accompanied by an increase in hemopoietic progenitors circulating in the blood and an increased uptake of these progenitors by the spleen. Similar results were obtained by treatment of the recipients with an antibody to vascular cell adhesion molecule 1 (VCAM-1), a ligand for VLA4. Furthermore, we showed that administration of the same antibodies (anti-VLA4 or anti-VCAM-1) to normal animals causes mobilization of hemopoietic progenitors into blood. These data suggest that hemopoietic cell lodgement in the BM is a regulatable process and can be influenced by VLA4/VCAM-1 adhesion pathway. Although additional molecular pathways are not excluded and may be likely, our data establish VCAM-1 as a BM endothelial addressin, analogous to the role that mucosal addressin cell adhesion molecule (MAdCAM) plays in lymphocyte homing. Whether splenic uptake of hemopoietic progenitors is passive or controlled through different mechanisms remains to be clarified. In addition, we provide experimental evidence that homing and mobilization are related phenomena involving, at least partly, similar molecular pathways.

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Selected References

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

  1. Aizawa S., Tavassoli M. Molecular basis of the recognition of intravenously transplanted hemopoietic cells by bone marrow. Proc Natl Acad Sci U S A. 1988 May;85(9):3180–3183. doi: 10.1073/pnas.85.9.3180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berlin C., Bargatze R. F., Campbell J. J., von Andrian U. H., Szabo M. C., Hasslen S. R., Nelson R. D., Berg E. L., Erlandsen S. L., Butcher E. C. alpha 4 integrins mediate lymphocyte attachment and rolling under physiologic flow. Cell. 1995 Feb 10;80(3):413–422. doi: 10.1016/0092-8674(95)90491-3. [DOI] [PubMed] [Google Scholar]
  3. Berlin C., Berg E. L., Briskin M. J., Andrew D. P., Kilshaw P. J., Holzmann B., Weissman I. L., Hamann A., Butcher E. C. Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell. 1993 Jul 16;74(1):185–195. doi: 10.1016/0092-8674(93)90305-a. [DOI] [PubMed] [Google Scholar]
  4. Carlos T. M., Harlan J. M. Leukocyte-endothelial adhesion molecules. Blood. 1994 Oct 1;84(7):2068–2101. [PubMed] [Google Scholar]
  5. Guan J. L., Hynes R. O. Lymphoid cells recognize an alternatively spliced segment of fibronectin via the integrin receptor alpha 4 beta 1. Cell. 1990 Jan 12;60(1):53–61. doi: 10.1016/0092-8674(90)90715-q. [DOI] [PubMed] [Google Scholar]
  6. Hénon P. R. Peripheral blood stem cell transplantations: past, present and future. Stem Cells. 1993 May;11(3):154–172. doi: 10.1002/stem.5530110302. [DOI] [PubMed] [Google Scholar]
  7. Kerst J. M., Sanders J. B., Slaper-Cortenbach I. C., Doorakkers M. C., Hooibrink B., van Oers R. H., von dem Borne A. E., van der Schoot C. E. Alpha 4 beta 1 and alpha 5 beta 1 are differentially expressed during myelopoiesis and mediate the adherence of human CD34+ cells to fibronectin in an activation-dependent way. Blood. 1993 Jan 15;81(2):344–351. [PubMed] [Google Scholar]
  8. Kinashi T., Springer T. A. Adhesion molecules in hematopoietic cells. Blood Cells. 1994;20(1):25–44. [PubMed] [Google Scholar]
  9. Kretchmar A. L., Conover W. R. Colony-forming cells in the spleen. Determination of the fraction transplanted. Transplantation. 1969 Nov;8(5):576–581. doi: 10.1097/00007890-196911000-00004. [DOI] [PubMed] [Google Scholar]
  10. Liesveld J. L., Winslow J. M., Frediani K. E., Ryan D. H., Abboud C. N. Expression of integrins and examination of their adhesive function in normal and leukemic hematopoietic cells. Blood. 1993 Jan 1;81(1):112–121. [PubMed] [Google Scholar]
  11. Long M. W. Blood cell cytoadhesion molecules. Exp Hematol. 1992 Mar;20(3):288–301. [PubMed] [Google Scholar]
  12. Lord B. I. The relationship between spleen colony production and spleen cellularity. Cell Tissue Kinet. 1971 May;4(3):211–216. doi: 10.1111/j.1365-2184.1971.tb01531.x. [DOI] [PubMed] [Google Scholar]
  13. Maggio-Price L., Wolf N. S., Priestley G. V., Pietrzyk M. E., Bernstein S. E. Evaluation of stem cell reserve using serial bone marrow transplantation and competitive repopulation in a murine model of chronic hemolytic anemia. Exp Hematol. 1988 Sep;16(8):653–659. [PubMed] [Google Scholar]
  14. Miyake K., Medina K., Ishihara K., Kimoto M., Auerbach R., Kincade P. W. A VCAM-like adhesion molecule on murine bone marrow stromal cells mediates binding of lymphocyte precursors in culture. J Cell Biol. 1991 Aug;114(3):557–565. doi: 10.1083/jcb.114.3.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Miyake K., Weissman I. L., Greenberger J. S., Kincade P. W. Evidence for a role of the integrin VLA-4 in lympho-hemopoiesis. J Exp Med. 1991 Mar 1;173(3):599–607. doi: 10.1084/jem.173.3.599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Papayannopoulou T., Nakamoto B. Peripheralization of hemopoietic progenitors in primates treated with anti-VLA4 integrin. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9374–9378. doi: 10.1073/pnas.90.20.9374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Penn P. E., Jiang D. Z., Fei R. G., Sitnicka E., Wolf N. S. Dissecting the hematopoietic microenvironment. IX. Further characterization of murine bone marrow stromal cells. Blood. 1993 Mar 1;81(5):1205–1213. [PubMed] [Google Scholar]
  18. 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]
  19. Samlowski W. E., Daynes R. A. Bone marrow engraftment efficiency is enhanced by competitive inhibition of the hepatic asialoglycoprotein receptor. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2508–2512. doi: 10.1073/pnas.82.8.2508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Siczkowski M., Clarke D., Gordon M. Y. Binding of primitive hematopoietic progenitor cells to marrow stromal cells involves heparan sulfate. Blood. 1992 Aug 15;80(4):912–919. [PubMed] [Google Scholar]
  21. Simmons P. J., Masinovsky B., Longenecker B. M., Berenson R., Torok-Storb B., Gallatin W. M. Vascular cell adhesion molecule-1 expressed by bone marrow stromal cells mediates the binding of hematopoietic progenitor cells. Blood. 1992 Jul 15;80(2):388–395. [PubMed] [Google Scholar]
  22. Springer T. A. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell. 1994 Jan 28;76(2):301–314. doi: 10.1016/0092-8674(94)90337-9. [DOI] [PubMed] [Google Scholar]
  23. Teixidó J., Hemler M. E., Greenberger J. S., Anklesaria P. Role of beta 1 and beta 2 integrins in the adhesion of human CD34hi stem cells to bone marrow stroma. J Clin Invest. 1992 Aug;90(2):358–367. doi: 10.1172/JCI115870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Tonelli Q., Meints R. H. Sialic acid: a specific role in hematopoietic spleen colony formation. J Supramol Struct. 1978;8(1):67–78. doi: 10.1002/jss.400080106. [DOI] [PubMed] [Google Scholar]
  25. Vos O., Buurman W. A., Ploemacher R. E. Mobilization of haemopoietic stem cells (CFU) into the peripheral blood of the mouse; effects of endotoxin and other compounds. Cell Tissue Kinet. 1972 Nov;5(6):467–479. doi: 10.1111/j.1365-2184.1972.tb00385.x. [DOI] [PubMed] [Google Scholar]
  26. Williams D. A., Rios M., Stephens C., Patel V. P. Fibronectin and VLA-4 in haematopoietic stem cell-microenvironment interactions. Nature. 1991 Aug 1;352(6334):438–441. doi: 10.1038/352438a0. [DOI] [PubMed] [Google Scholar]
  27. Wolf N. S. Dissecting the hematopoietic microenvironment. I. Stem cell lodgment and commitment, and the proliferation and differentiation of erythropoietic descendants in the S1-S1d mouse. Cell Tissue Kinet. 1974 Jan;7(1):89–98. doi: 10.1111/j.1365-2184.1974.tb00402.x. [DOI] [PubMed] [Google Scholar]
  28. Wolf N. S., Priestley G. V. Kinetics of early and late spleen colony development. Exp Hematol. 1986 Aug;14(7):676–682. [PubMed] [Google Scholar]

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