Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1991 Mar 1;173(3):599–607. doi: 10.1084/jem.173.3.599

Evidence for a role of the integrin VLA-4 in lympho-hemopoiesis

PMCID: PMC2118814  PMID: 1997648

Abstract

Adhesion molecules are probably required for retention of maturing lymphocyte precursors in bone marrow, where they closely interact with and are dependent on stromal cells. Lymphomyeloid cell lines avidly adhere to cloned stromal cell lines in culture and screening pairs of these resulted in a selection strategy for a new monoclonal antibody to a leukocyte adhesion molecule. Immunoprecipitation analyses and comparison to a previously described antibody showed that it recognizes the alpha 4 chain of the integrin, VLA-4. This antibody totally inhibited lymphopoiesis and retarded myelopoiesis in long-term bone marrow cultures. A similar selection strategy resulted in two additional antibodies which define a single 100-kD species on stromal cells. This stromal cell adhesion molecule is a potential counter- receptor/ligand for VLA-4 on murine lympho-myeloid cells. Our findings suggest a new role for VLA-4 in lymphoid progenitor-microenvironment interactions. Recognition molecules that function in cell migration and inflammation in peripheral tissues may be important for steady-state lymphopoiesis within bone marrow.

Full Text

The Full Text of this article is available as a PDF (1.0 MB).

Selected References

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

  1. Anklesaria P., Klassen V., Sakakeeny M. A., FitzGerald T. J., Harrison D., Rybak M. E., Greenberger J. S. Biological characterization of cloned permanent stromal cell lines from anemic Sl/Sld mice and +/+ littermates. Exp Hematol. 1987 Jul;15(6):636–644. [PubMed] [Google Scholar]
  2. Bernardi P., Patel V. P., Lodish H. F. Lymphoid precursor cells adhere to two different sites on fibronectin. J Cell Biol. 1987 Jul;105(1):489–498. doi: 10.1083/jcb.105.1.489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Campbell A. D., Long M. W., Wicha M. S. Haemonectin, a bone marrow adhesion protein specific for cells of granulocyte lineage. Nature. 1987 Oct 22;329(6141):744–746. doi: 10.1038/329744a0. [DOI] [PubMed] [Google Scholar]
  4. Cell J. W. Anglo-Indian medical theory and the origins of segregation in West Africa. Am Hist Rev. 1986 Apr;91(2):307–335. [PubMed] [Google Scholar]
  5. Collins L. S., Dorshkind K. A stromal cell line from myeloid long-term bone marrow cultures can support myelopoiesis and B lymphopoiesis. J Immunol. 1987 Feb 15;138(4):1082–1087. [PubMed] [Google Scholar]
  6. Dexter T. M., Allen T. D., Lajtha L. G. Conditions controlling the proliferation of haemopoietic stem cells in vitro. J Cell Physiol. 1977 Jun;91(3):335–344. doi: 10.1002/jcp.1040910303. [DOI] [PubMed] [Google Scholar]
  7. Dustin M. L., Springer T. A. T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1. Nature. 1989 Oct 19;341(6243):619–624. doi: 10.1038/341619a0. [DOI] [PubMed] [Google Scholar]
  8. Elices M. J., Osborn L., Takada Y., Crouse C., Luhowskyj S., Hemler M. E., Lobb R. R. VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site. Cell. 1990 Feb 23;60(4):577–584. doi: 10.1016/0092-8674(90)90661-w. [DOI] [PubMed] [Google Scholar]
  9. Engelhard D., Landreth K. S., Kapoor N., Kincade P. W., De Bault L. E., Theodore A., Good R. A. Cycling of peripheral blood and marrow lymphocytes in cyclic neutropenia. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5734–5738. doi: 10.1073/pnas.80.18.5734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Freedman A. S., Munro J. M., Rice G. E., Bevilacqua M. P., Morimoto C., McIntyre B. W., Rhynhart K., Pober J. S., Nadler L. M. Adhesion of human B cells to germinal centers in vitro involves VLA-4 and INCAM-110. Science. 1990 Aug 31;249(4972):1030–1033. doi: 10.1126/science.1697696. [DOI] [PubMed] [Google Scholar]
  11. Garcia-Pardo A., Wayner E. A., Carter W. G., Ferreira O. C., Jr Human B lymphocytes define an alternative mechanism of adhesion to fibronectin. The interaction of the alpha 4 beta 1 integrin with the LHGPEILDVPST sequence of the type III connecting segment is sufficient to promote cell attachment. J Immunol. 1990 May 1;144(9):3361–3366. [PubMed] [Google Scholar]
  12. Gimble J. M., Pietrangeli C., Henley A., Dorheim M. A., Silver J., Namen A., Takeichi M., Goridis C., Kincade P. W. Characterization of murine bone marrow and spleen-derived stromal cells: analysis of leukocyte marker and growth factor mRNA transcript levels. Blood. 1989 Jul;74(1):303–311. [PubMed] [Google Scholar]
  13. Hayashi S., Gimble J. M., Henley A., Ellingsworth L. R., Kincade P. W. Differential effects of TGF-beta 1 on lymphohemopoiesis in long-term bone marrow cultures. Blood. 1989 Oct;74(5):1711–1717. [PubMed] [Google Scholar]
  14. Hemler M. E., Huang C., Takada Y., Schwarz L., Strominger J. L., Clabby M. L. Characterization of the cell surface heterodimer VLA-4 and related peptides. J Biol Chem. 1987 Aug 25;262(24):11478–11485. [PubMed] [Google Scholar]
  15. Hemler M. E. VLA proteins in the integrin family: structures, functions, and their role on leukocytes. Annu Rev Immunol. 1990;8:365–400. doi: 10.1146/annurev.iy.08.040190.002053. [DOI] [PubMed] [Google Scholar]
  16. Kina T., Majumdar A. S., Heimfeld S., Kaneshima H., Holzmann B., Katsura Y., Weissman I. L. Identification of a 107-kD glycoprotein that mediates adhesion between stromal cells and hematolymphoid cells. J Exp Med. 1991 Feb 1;173(2):373–381. doi: 10.1084/jem.173.2.373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kincade P. W. Experimental models for understanding B lymphocyte formation. Adv Immunol. 1987;41:181–267. doi: 10.1016/s0065-2776(08)60032-2. [DOI] [PubMed] [Google Scholar]
  18. Kincade P. W., Lee G., Pietrangeli C. E., Hayashi S., Gimble J. M. Cells and molecules that regulate B lymphopoiesis in bone marrow. Annu Rev Immunol. 1989;7:111–143. doi: 10.1146/annurev.iy.07.040189.000551. [DOI] [PubMed] [Google Scholar]
  19. Kincade P. W., Lee G., Watanabe T., Sun L., Scheid M. P. Antigens displayed on murine B lymphocyte precursors. J Immunol. 1981 Dec;127(6):2262–2268. [PubMed] [Google Scholar]
  20. Lesley J., Schulte R., Hyman R. Binding of hyaluronic acid to lymphoid cell lines is inhibited by monoclonal antibodies against Pgp-1. Exp Cell Res. 1990 Apr;187(2):224–233. doi: 10.1016/0014-4827(90)90085-o. [DOI] [PubMed] [Google Scholar]
  21. Lo S. K., Detmers P. A., Levin S. M., Wright S. D. Transient adhesion of neutrophils to endothelium. J Exp Med. 1989 May 1;169(5):1779–1793. doi: 10.1084/jem.169.5.1779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. McIntyre B. W., Evans E. L., Bednarczyk J. L. Lymphocyte surface antigen L25 is a member of the integrin receptor superfamily. J Biol Chem. 1989 Aug 15;264(23):13745–13750. [PubMed] [Google Scholar]
  23. Miyake K., Kincade P. W. A new cell adhesion mechanism involving hyaluronate and CD44. Curr Top Microbiol Immunol. 1990;166:87–90. doi: 10.1007/978-3-642-75889-8_12. [DOI] [PubMed] [Google Scholar]
  24. Miyake K., Medina K. L., Hayashi S., Ono S., Hamaoka T., Kincade P. W. Monoclonal antibodies to Pgp-1/CD44 block lympho-hemopoiesis in long-term bone marrow cultures. J Exp Med. 1990 Feb 1;171(2):477–488. doi: 10.1084/jem.171.2.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Miyake K., Underhill C. B., Lesley J., Kincade P. W. Hyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition. J Exp Med. 1990 Jul 1;172(1):69–75. doi: 10.1084/jem.172.1.69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Osborn L., Hession C., Tizard R., Vassallo C., Luhowskyj S., Chi-Rosso G., Lobb R. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell. 1989 Dec 22;59(6):1203–1211. doi: 10.1016/0092-8674(89)90775-7. [DOI] [PubMed] [Google Scholar]
  27. Paige C. J., Kincade P. W., Ralph P. Murine B cell leukemia line with inducible surface immunoglobulin expression. J Immunol. 1978 Aug;121(2):641–647. [PubMed] [Google Scholar]
  28. Patel V. P., Ciechanover A., Platt O., Lodish H. F. Mammalian reticulocytes lose adhesion to fibronectin during maturation to erythrocytes. Proc Natl Acad Sci U S A. 1985 Jan;82(2):440–444. doi: 10.1073/pnas.82.2.440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rice G. E., Bevilacqua M. P. An inducible endothelial cell surface glycoprotein mediates melanoma adhesion. Science. 1989 Dec 8;246(4935):1303–1306. doi: 10.1126/science.2588007. [DOI] [PubMed] [Google Scholar]
  30. Schwartz B. R., Wayner E. A., Carlos T. M., Ochs H. D., Harlan J. M. Identification of surface proteins mediating adherence of CD11/CD18-deficient lymphoblastoid cells to cultured human endothelium. J Clin Invest. 1990 Jun;85(6):2019–2022. doi: 10.1172/JCI114668. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sánchez-Madrid F., De Landázuri M. O., Morago G., Cebrián M., Acevedo A., Bernabeu C. VLA-3: a novel polypeptide association within the VLA molecular complex: cell distribution and biochemical characterization. Eur J Immunol. 1986 Nov;16(11):1343–1349. doi: 10.1002/eji.1830161106. [DOI] [PubMed] [Google Scholar]
  32. Thomas P. S., Pietrangeli C. E., Hayashi S., Schachner M., Goridis C., Low M., Kincade P. W. Demonstration of neural cell adhesion molecules on stromal cells that support lymphopoiesis. Leukemia. 1988 Mar;2(3):171–175. [PubMed] [Google Scholar]
  33. Wayner E. A., Garcia-Pardo A., Humphries M. J., McDonald J. A., Carter W. G. Identification and characterization of the T lymphocyte adhesion receptor for an alternative cell attachment domain (CS-1) in plasma fibronectin. J Cell Biol. 1989 Sep;109(3):1321–1330. doi: 10.1083/jcb.109.3.1321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Whitlock C. A., Witte O. N. Long-term culture of B lymphocytes and their precursors from murine bone marrow. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3608–3612. doi: 10.1073/pnas.79.11.3608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Witte P. L., Robinson M., Henley A., Low M. G., Stiers D. L., Perkins S., Fleischman R. A., Kincade P. W. Relationships between B-lineage lymphocytes and stromal cells in long-term bone marrow cultures. Eur J Immunol. 1987 Oct;17(10):1473–1484. doi: 10.1002/eji.1830171014. [DOI] [PubMed] [Google Scholar]
  36. van Kooyk Y., van de Wiel-van Kemenade P., Weder P., Kuijpers T. W., Figdor C. G. Enhancement of LFA-1-mediated cell adhesion by triggering through CD2 or CD3 on T lymphocytes. Nature. 1989 Dec 14;342(6251):811–813. doi: 10.1038/342811a0. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES