Skip to main content
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1991 Aug 1;114(3):557–565. doi: 10.1083/jcb.114.3.557

A VCAM-like adhesion molecule on murine bone marrow stromal cells mediates binding of lymphocyte precursors in culture

PMCID: PMC2289098  PMID: 1713592

Abstract

Two new mAbs (M/K-1 and M/K-2) define an adhesion molecule expressed on stromal cell clones derived from murine bone marrow. The protein is similar in size to a human endothelial cell adhesion molecule known as VCAM-1 or INCAM110. VCAM-1 is expressed on endothelial cells in inflammatory sites and recognized by the integrin VLA-4 expressed on lymphocytes and monocytes. The new stromal cell molecule is a candidate ligand for the VLA-4 expressed on immature B lineage lymphocytes and a possible homologue of human VCAM-1. We now report additional similarities in the distribution, structure, and function of these proteins. The M/K antibodies detected large cells in normal bone marrow, as well as rare cells in other tissues. The antigen was constitutively expressed and functioned as a cell adhesion molecule on cultured murine endothelial cells. It correlated with the presence of mRNA which hybridized to a human VCAM-1 cDNA probe. Partial NH2 terminal amino acid sequencing of the murine protein revealed similarities to VCAM-1 and attachment of human lymphoma cells to murine endothelial cell lines was inhibited by the M/K antibodies. All of these observations suggest that the murine and human cell adhesion proteins may be related. The antibodies selectively interfered with B lymphocyte formation when included in long term bone marrow cultures. Moreover, they caused rapid detachment of lymphocytes from the adherent layer when added to preestablished cultures. The VCAM-like cell adhesion molecule on stromal cells and VLA-4 on lymphocyte precursors may both be important for B lymphocyte formation.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

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

  1. Allavena P., Paganin C., Martin-Padura I., Peri G., Gaboli M., Dejana E., Marchisio P. C., Mantovani A. Molecules and structures involved in the adhesion of natural killer cells to vascular endothelium. J Exp Med. 1991 Feb 1;173(2):439–448. doi: 10.1084/jem.173.2.439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Altieri D. C., Edgington T. S. A monoclonal antibody reacting with distinct adhesion molecules defines a transition in the functional state of the receptor CD11b/CD18 (Mac-1). J Immunol. 1988 Oct 15;141(8):2656–2660. [PubMed] [Google Scholar]
  3. 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]
  4. Auerbach R., Lu W. C., Pardon E., Gumkowski F., Kaminska G., Kaminski M. Specificity of adhesion between murine tumor cells and capillary endothelium: an in vitro correlate of preferential metastasis in vivo. Cancer Res. 1987 Mar 15;47(6):1492–1496. [PubMed] [Google Scholar]
  5. 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]
  6. Briscoe D. M., Schoen F. J., Rice G. E., Bevilacqua M. P., Ganz P., Pober J. S. Induced expression of endothelial-leukocyte adhesion molecules in human cardiac allografts. Transplantation. 1991 Feb;51(2):537–539. [PubMed] [Google Scholar]
  7. 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]
  8. Carlos T. M., Schwartz B. R., Kovach N. L., Yee E., Rosa M., Osborn L., Chi-Rosso G., Newman B., Lobb R., Rosso M. Vascular cell adhesion molecule-1 mediates lymphocyte adherence to cytokine-activated cultured human endothelial cells. Blood. 1990 Sep 1;76(5):965–970. [PubMed] [Google Scholar]
  9. Carter W. G., Wayner E. A. Characterization of the class III collagen receptor, a phosphorylated, transmembrane glycoprotein expressed in nucleated human cells. J Biol Chem. 1988 Mar 25;263(9):4193–4201. [PubMed] [Google Scholar]
  10. Couture C., Patel P. C., Potworowski E. F. A novel thymic epithelial adhesion molecule. Eur J Immunol. 1990 Dec;20(12):2769–2773. doi: 10.1002/eji.1830201235. [DOI] [PubMed] [Google Scholar]
  11. Denning S. M., Le P. T., Singer K. H., Haynes B. F. Antibodies against the CD44 p80, lymphocyte homing receptor molecule augment human peripheral blood T cell activation. J Immunol. 1990 Jan 1;144(1):7–15. [PubMed] [Google Scholar]
  12. 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]
  13. Figdor C. G., van Kooyk Y., Keizer G. D. On the mode of action of LFA-1. Immunol Today. 1990 Aug;11(8):277–280. doi: 10.1016/0167-5699(90)90112-m. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Gallatin W. M., Wayner E. A., Hoffman P. A., St John T., Butcher E. C., Carter W. G. Structural homology between lymphocyte receptors for high endothelium and class III extracellular matrix receptor. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4654–4658. doi: 10.1073/pnas.86.12.4654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. 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]
  18. Gismondi A., Morrone S., Humphries M. J., Piccoli M., Frati L., Santoni A. Human natural killer cells express VLA-4 and VLA-5, which mediate their adhesion to fibronectin. J Immunol. 1991 Jan 1;146(1):384–392. [PubMed] [Google Scholar]
  19. Gordon M. Y., Clarke D., Atkinson J., Greaves M. F. Hemopoietic progenitor cell binding to the stromal microenvironment in vitro. Exp Hematol. 1990 Aug;18(7):837–842. [PubMed] [Google Scholar]
  20. Graber N., Gopal T. V., Wilson D., Beall L. D., Polte T., Newman W. T cells bind to cytokine-activated endothelial cells via a novel, inducible sialoglycoprotein and endothelial leukocyte adhesion molecule-1. J Immunol. 1990 Aug 1;145(3):819–830. [PubMed] [Google Scholar]
  21. 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]
  22. He H. T., Naquet P., Caillol D., Pierres M. Thy-1 supports adhesion of mouse thymocytes to thymic epithelial cells through a Ca2(+)-independent mechanism. J Exp Med. 1991 Feb 1;173(2):515–518. doi: 10.1084/jem.173.2.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hession C., Tizard R., Vassallo C., Schiffer S. B., Goff D., Moy P., Chi-Rosso G., Luhowskyj S., Lobb R., Osborn L. Cloning of an alternate form of vascular cell adhesion molecule-1 (VCAM1). J Biol Chem. 1991 Apr 15;266(11):6682–6685. [PubMed] [Google Scholar]
  24. Holzmann B., McIntyre B. W., Weissman I. L. Identification of a murine Peyer's patch--specific lymphocyte homing receptor as an integrin molecule with an alpha chain homologous to human VLA-4 alpha. Cell. 1989 Jan 13;56(1):37–46. doi: 10.1016/0092-8674(89)90981-1. [DOI] [PubMed] [Google Scholar]
  25. Holzmann B., Weissman I. L. Peyer's patch-specific lymphocyte homing receptors consist of a VLA-4-like alpha chain associated with either of two integrin beta chains, one of which is novel. EMBO J. 1989 Jun;8(6):1735–1741. doi: 10.1002/j.1460-2075.1989.tb03566.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Huet S., Groux H., Caillou B., Valentin H., Prieur A. M., Bernard A. CD44 contributes to T cell activation. J Immunol. 1989 Aug 1;143(3):798–801. [PubMed] [Google Scholar]
  27. 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]
  28. 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]
  29. 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]
  30. Lemoine F. M., Dedhar S., Lima G. M., Eaves C. J. Transformation-associated alterations in interactions between pre-B cells and fibronectin. Blood. 1990 Dec 1;76(11):2311–2320. [PubMed] [Google Scholar]
  31. 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]
  32. Liesveld J. L., Winslow J. M., Kempski M. C., Ryan D. H., Brennan J. K., Abboud C. N. Adhesive interactions of normal and leukemic human CD34+ myeloid progenitors: role of marrow stromal, fibroblast, and cytomatrix components. Exp Hematol. 1991 Jan;19(1):63–70. [PubMed] [Google Scholar]
  33. Low M. G., Stiernberg J., Waneck G. L., Flavell R. A., Kincade P. W. Cell-specific heterogeneity in sensitivity of phosphatidylinositol-anchored membrane antigens to release by phospholipase C. J Immunol Methods. 1988 Oct 4;113(1):101–111. doi: 10.1016/0022-1759(88)90386-9. [DOI] [PubMed] [Google Scholar]
  34. Masinovsky B., Urdal D., Gallatin W. M. IL-4 acts synergistically with IL-1 beta to promote lymphocyte adhesion to microvascular endothelium by induction of vascular cell adhesion molecule-1. J Immunol. 1990 Nov 1;145(9):2886–2895. [PubMed] [Google Scholar]
  35. 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]
  36. 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]
  37. 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]
  38. Nojima Y., Humphries M. J., Mould A. P., Komoriya A., Yamada K. M., Schlossman S. F., Morimoto C. VLA-4 mediates CD3-dependent CD4+ T cell activation via the CS1 alternatively spliced domain of fibronectin. J Exp Med. 1990 Oct 1;172(4):1185–1192. doi: 10.1084/jem.172.4.1185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. O'Toole T. E., Loftus J. C., Du X. P., Glass A. A., Ruggeri Z. M., Shattil S. J., Plow E. F., Ginsberg M. H. Affinity modulation of the alpha IIb beta 3 integrin (platelet GPIIb-IIIa) is an intrinsic property of the receptor. Cell Regul. 1990 Nov;1(12):883–893. doi: 10.1091/mbc.1.12.883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Obeso J., Weber J., Auerbach R. A hemangioendothelioma-derived cell line: its use as a model for the study of endothelial cell biology. Lab Invest. 1990 Aug;63(2):259–269. [PubMed] [Google Scholar]
  41. 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]
  42. Osborn L. Leukocyte adhesion to endothelium in inflammation. Cell. 1990 Jul 13;62(1):3–6. doi: 10.1016/0092-8674(90)90230-c. [DOI] [PubMed] [Google Scholar]
  43. Patel V. P., Lodish H. F. The fibronectin receptor on mammalian erythroid precursor cells: characterization and developmental regulation. J Cell Biol. 1986 Feb;102(2):449–456. doi: 10.1083/jcb.102.2.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Picker L. J., Nakache M., Butcher E. C. Monoclonal antibodies to human lymphocyte homing receptors define a novel class of adhesion molecules on diverse cell types. J Cell Biol. 1989 Aug;109(2):927–937. doi: 10.1083/jcb.109.2.927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Polte T., Newman W., Gopal T. V. Full length vascular cell adhesion molecule 1 (VCAM-1). Nucleic Acids Res. 1990 Oct 11;18(19):5901–5901. doi: 10.1093/nar/18.19.5901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Reiser H., Oettgen H., Yeh E. T., Terhorst C., Low M. G., Benacerraf B., Rock K. L. Structural characterization of the TAP molecule: a phosphatidylinositol-linked glycoprotein distinct from the T cell receptor/T3 complex and Thy-1. Cell. 1986 Nov 7;47(3):365–370. doi: 10.1016/0092-8674(86)90593-3. [DOI] [PubMed] [Google Scholar]
  47. 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]
  48. Rice G. E., Munro J. M., Bevilacqua M. P. Inducible cell adhesion molecule 110 (INCAM-110) is an endothelial receptor for lymphocytes. A CD11/CD18-independent adhesion mechanism. J Exp Med. 1990 Apr 1;171(4):1369–1374. doi: 10.1084/jem.171.4.1369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Rice G. E., Munro J. M., Corless C., Bevilacqua M. P. Vascular and nonvascular expression of INCAM-110. A target for mononuclear leukocyte adhesion in normal and inflamed human tissues. Am J Pathol. 1991 Feb;138(2):385–393. [PMC free article] [PubMed] [Google Scholar]
  50. Rosemblatt M., Vuillet-Gaugler M. H., Leroy C., Coulombel L. Coexpression of two fibronectin receptors, VLA-4 and VLA-5, by immature human erythroblastic precursor cells. J Clin Invest. 1991 Jan;87(1):6–11. doi: 10.1172/JCI115002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Ruoslahti E. Integrins. J Clin Invest. 1991 Jan;87(1):1–5. doi: 10.1172/JCI114957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Ryan D. H., Nuccie B. L., Abboud C. N., Liesveld J. L. Maturation-dependent adhesion of human B cell precursors to the bone marrow microenvironment. J Immunol. 1990 Jul 15;145(2):477–484. [PubMed] [Google Scholar]
  53. 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]
  54. Shimizu Y., Van Seventer G. A., Horgan K. J., Shaw S. Regulated expression and binding of three VLA (beta 1) integrin receptors on T cells. Nature. 1990 May 17;345(6272):250–253. doi: 10.1038/345250a0. [DOI] [PubMed] [Google Scholar]
  55. Shimizu Y., Van Seventer G. A., Siraganian R., Wahl L., Shaw S. Dual role of the CD44 molecule in T cell adhesion and activation. J Immunol. 1989 Oct 15;143(8):2457–2463. [PubMed] [Google Scholar]
  56. Shimizu Y., van Seventer G. A., Horgan K. J., Shaw S. Costimulation of proliferative responses of resting CD4+ T cells by the interaction of VLA-4 and VLA-5 with fibronectin or VLA-6 with laminin. J Immunol. 1990 Jul 1;145(1):59–67. [PubMed] [Google Scholar]
  57. Siu G., Hedrick S. M., Brian A. A. Isolation of the murine intercellular adhesion molecule 1 (ICAM-1) gene. ICAM-1 enhances antigen-specific T cell activation. J Immunol. 1989 Dec 1;143(11):3813–3820. [PubMed] [Google Scholar]
  58. Soligo D., Schiró R., Luksch R., Manara G., Quirici N., Parravicini C., Lambertenghi Deliliers G. Expression of integrins in human bone marrow. Br J Haematol. 1990 Nov;76(3):323–332. doi: 10.1111/j.1365-2141.1990.tb06363.x. [DOI] [PubMed] [Google Scholar]
  59. Springer T. A. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. doi: 10.1038/346425a0. [DOI] [PubMed] [Google Scholar]
  60. Sudo T., Ito M., Ogawa Y., Iizuka M., Kodama H., Kunisada T., Hayashi S., Ogawa M., Sakai K., Nishikawa S. Interleukin 7 production and function in stromal cell-dependent B cell development. J Exp Med. 1989 Jul 1;170(1):333–338. doi: 10.1084/jem.170.1.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. 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]
  62. Thornhill M. H., Wellicome S. M., Mahiouz D. L., Lanchbury J. S., Kyan-Aung U., Haskard D. O. Tumor necrosis factor combines with IL-4 or IFN-gamma to selectively enhance endothelial cell adhesiveness for T cells. The contribution of vascular cell adhesion molecule-1-dependent and -independent binding mechanisms. J Immunol. 1991 Jan 15;146(2):592–598. [PubMed] [Google Scholar]
  63. 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]
  64. Webb D. S., Shimizu Y., Van Seventer G. A., Shaw S., Gerrard T. L. LFA-3, CD44, and CD45: physiologic triggers of human monocyte TNF and IL-1 release. Science. 1990 Sep 14;249(4974):1295–1297. doi: 10.1126/science.1697984. [DOI] [PubMed] [Google Scholar]
  65. 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]
  66. 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]
  67. Zuckerman K. S., Rhodes R. K., Goodrum D. D., Patel V. R., Sparks B., Wells J., Wicha M. S., Mayo L. A. Inhibition of collagen deposition in the extracellular matrix prevents the establishment of a stroma supportive of hematopoiesis in long-term murine bone marrow cultures. J Clin Invest. 1985 Mar;75(3):970–975. doi: 10.1172/JCI111798. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES