Abstract
We have characterized the adhesion molecule HEMCAM, which is expressed by hemopoietic progenitors of embryonic bone marrow. HEMCAM belongs to the immunoglobulin superfamily and consists of the V-V-C2-C2-C2 Ig domains. There are three mRNA splice variants. One has a short cytoplasmic tail; another has a long tail; while the third seems to lack transmembrane and cytoplasmic regions. Except for the NH2-terminal sequence, HEMCAM is identical to gicerin, a molecular involved in neurite outgrowth and Wilm's kidney tumor progression in the chicken and it is significantly homologous with MUC18 a molecule involved in melanoma progression and metastasis in human beings. In the bone marrow the HEMCAM+ cell population contains c-kit+ subsets. HEMCAM+ cells coexpressing the receptor tyrosine kinase c-kit give rise to T cells at a frequency of 0.17 when injected intrathymically in congenic animals. As HEMCAM+, c-kit+ cells differentiate into myeloid and erythroid CFU's the double-positive cell population seems to contain precursors for multiple lineages. HEMCAM promotes cell-cell adhesion of transfected cells. Cross-linking of murine HEMCAM leads to cell spreading of T- lymphocyte progenitors adhering to the vascular adhesion molecules, PECAM-1 and VCAM-1. Thus, HEMCAM is likely to be involved in cellular adhesion and homing processes.
Full Text
The Full Text of this article is available as a PDF (5.4 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bott C. M., Doshi J. B., Morimoto C., Romain P. L., Fox D. A. Activation of human T cells through CD6: functional effects of a novel anti-CD6 monoclonal antibody and definition of four epitopes of the CD6 glycoprotein. Int Immunol. 1993 Jul;5(7):783–792. doi: 10.1093/intimm/5.7.783. [DOI] [PubMed] [Google Scholar]
- Bowen M. A., Patel D. D., Li X., Modrell B., Malacko A. R., Wang W. C., Marquardt H., Neubauer M., Pesando J. M., Francke U. Cloning, mapping, and characterization of activated leukocyte-cell adhesion molecule (ALCAM), a CD6 ligand. J Exp Med. 1995 Jun 1;181(6):2213–2220. doi: 10.1084/jem.181.6.2213. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burns F. R., von Kannen S., Guy L., Raper J. A., Kamholz J., Chang S. DM-GRASP, a novel immunoglobulin superfamily axonal surface protein that supports neurite extension. Neuron. 1991 Aug;7(2):209–220. doi: 10.1016/0896-6273(91)90259-3. [DOI] [PubMed] [Google Scholar]
- Campbell I. G., Foulkes W. D., Senger G., Trowsdale J., Garin-Chesa P., Rettig W. J. Molecular cloning of the B-CAM cell surface glycoprotein of epithelial cancers: a novel member of the immunoglobulin superfamily. Cancer Res. 1994 Nov 15;54(22):5761–5765. [PubMed] [Google Scholar]
- Coltey M., Jotereau F. V., Le Douarin N. M. Evidence for a cyclic renewal of lymphocyte precursor cells in the embryonic chick thymus. Cell Differ. 1987 Nov;22(1):71–82. doi: 10.1016/0045-6039(87)90414-3. [DOI] [PubMed] [Google Scholar]
- Corbel C., Bluestein H. G., Pourquie O., Vaigot P., Le Douarin N. M. An antigen expressed by avian neuronal cells is also expressed by activated T lymphocytes. Cell Immunol. 1992 Apr 15;141(1):99–110. doi: 10.1016/0008-8749(92)90130-h. [DOI] [PubMed] [Google Scholar]
- Corbel C., Cormier F., Pourquie O., Bluestein H. G. BEN, a novel surface molecule of the immunoglobulin superfamily on avian hemopoietic progenitor cells shared with neural cells. Exp Cell Res. 1992 Nov;203(1):91–99. doi: 10.1016/0014-4827(92)90043-8. [DOI] [PubMed] [Google Scholar]
- Cormier F., Dieterlen-Lièvre F. The wall of the chick embryo aorta harbours M-CFC, G-CFC, GM-CFC and BFU-E. Development. 1988 Feb;102(2):279–285. doi: 10.1242/dev.102.2.279. [DOI] [PubMed] [Google Scholar]
- Dunon D., Imhof B. A. Mechanisms of thymus homing. Blood. 1993 Jan 1;81(1):1–8. [PubMed] [Google Scholar]
- Dunon D., Kaufman J., Salomonsen J., Skjoedt K., Vainio O., Thiery J. P., Imhof B. A. T cell precursor migration towards beta 2-microglobulin is involved in thymus colonization of chicken embryos. EMBO J. 1990 Oct;9(10):3315–3322. doi: 10.1002/j.1460-2075.1990.tb07531.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dunon D., Schwager J., Dangy J. P., Cooper M. D., Imhof B. A. T cell migration during development: homing is not related to TCR V beta 1 repertoire selection. EMBO J. 1994 Feb 15;13(4):808–815. doi: 10.1002/j.1460-2075.1994.tb06323.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dunon D., Schwager J., Dangy J. P., Imhof B. A. Ontogeny of TCR V beta 1 expression revealed novel invariant alternative transcripts. J Immunol. 1995 Feb 1;154(3):1256–1264. [PubMed] [Google Scholar]
- Gearing A. J., Newman W. Circulating adhesion molecules in disease. Immunol Today. 1993 Oct;14(10):506–512. doi: 10.1016/0167-5699(93)90267-O. [DOI] [PubMed] [Google Scholar]
- Graf T., McNagny K., Brady G., Frampton J. Chicken "erythroid" cells transformed by the Gag-Myb-Ets-encoding E26 leukemia virus are multipotent. Cell. 1992 Jul 24;70(2):201–213. doi: 10.1016/0092-8674(92)90096-u. [DOI] [PubMed] [Google Scholar]
- Gum J. R., Byrd J. C., Hicks J. W., Toribara N. W., Lamport D. T., Kim Y. S. Molecular cloning of human intestinal mucin cDNAs. Sequence analysis and evidence for genetic polymorphism. J Biol Chem. 1989 Apr 15;264(11):6480–6487. [PubMed] [Google Scholar]
- Günthert U., Hofmann M., Rudy W., Reber S., Zöller M., Haussmann I., Matzku S., Wenzel A., Ponta H., Herrlich P. A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell. 1991 Apr 5;65(1):13–24. doi: 10.1016/0092-8674(91)90403-l. [DOI] [PubMed] [Google Scholar]
- Hayashi Y., Miki N. Purification and characterization of a neurite outgrowth factor from chicken gizzard smooth muscle. J Biol Chem. 1985 Nov 15;260(26):14269–14278. [PubMed] [Google Scholar]
- Houssaint E., Mansikka A., Vainio O. Early separation of B and T lymphocyte precursors in chick embryo. J Exp Med. 1991 Aug 1;174(2):397–406. doi: 10.1084/jem.174.2.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ikuta K., Uchida N., Friedman J., Weissman I. L. Lymphocyte development from stem cells. Annu Rev Immunol. 1992;10:759–783. doi: 10.1146/annurev.iy.10.040192.003551. [DOI] [PubMed] [Google Scholar]
- Imhof B. A., Dunon D. Leukocyte migration and adhesion. Adv Immunol. 1995;58:345–416. doi: 10.1016/s0065-2776(08)60623-9. [DOI] [PubMed] [Google Scholar]
- Jürgens J. B., Gartland L. A., Du Pasquier L., Horton J. D., Göbel T. W., Cooper M. D. Identification of a candidate CD5 homologue in the amphibian Xenopus laevis. J Immunol. 1995 Nov 1;155(9):4218–4223. [PubMed] [Google Scholar]
- KAPLOW L. S. SIMPLIFIED MYELOPEROXIDASE STAIN USING BENZIDINE DIHYDROCHLORIDE. Blood. 1965 Aug;26:215–219. [PubMed] [Google Scholar]
- Keller G., Kennedy M., Papayannopoulou T., Wiles M. V. Hematopoietic commitment during embryonic stem cell differentiation in culture. Mol Cell Biol. 1993 Jan;13(1):473–486. doi: 10.1128/mcb.13.1.473. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kirkman R. L., Araujo J. L., Busch G. J., Carpenter C. B., Milford E. L., Reinherz E. L., Schlossman S. F., Strom T. B., Tilney N. L. Treatment of acute renal allograft rejection with monoclonal anti-T12 antibody. Transplantation. 1983 Dec;36(6):620–626. doi: 10.1097/00007890-198336060-00005. [DOI] [PubMed] [Google Scholar]
- Laessing U., Giordano S., Stecher B., Lottspeich F., Stuermer C. A. Molecular characterization of fish neurolin: a growth-associated cell surface protein and member of the immunoglobulin superfamily in the fish retinotectal system with similarities to chick protein DM-GRASP/SC-1/BEN. Differentiation. 1994 Apr;56(1-2):21–29. doi: 10.1046/j.1432-0436.1994.56120021.x. [DOI] [PubMed] [Google Scholar]
- Lanotte M. Terminal differentiation of hemopoietic cell clones cultured in tridimensional collagen matrix: in situ cell morphology and enzyme histochemistry analysis. Biol Cell. 1984;50(2):107–120. doi: 10.1111/j.1768-322x.1984.tb00257.x. [DOI] [PubMed] [Google Scholar]
- Lehmann J. M., Riethmüller G., Johnson J. P. MUC18, a marker of tumor progression in human melanoma, shows sequence similarity to the neural cell adhesion molecules of the immunoglobulin superfamily. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9891–9895. doi: 10.1073/pnas.86.24.9891. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leutz A., Beug H., Graf T. Purification and characterization of cMGF, a novel chicken myelomonocytic growth factor. EMBO J. 1984 Dec 20;3(13):3191–3197. doi: 10.1002/j.1460-2075.1984.tb02278.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Luhtala M., Koskinen R., Toivanen P., Vainio O. Characterization of chicken CD8-specific monoclonal antibodies recognizing novel epitopes. Scand J Immunol. 1995 Jul;42(1):171–174. doi: 10.1111/j.1365-3083.1995.tb03641.x. [DOI] [PubMed] [Google Scholar]
- Luhtala M., Salomonsen J., Hirota Y., Onodera T., Toivanen P., Vainio O. Analysis of chicken CD4 by monoclonal antibodies indicates evolutionary conservation between avian and mammalian species. Hybridoma. 1993 Dec;12(6):633–646. doi: 10.1089/hyb.1993.12.633. [DOI] [PubMed] [Google Scholar]
- McLeod D. L., Shreeve M. M., Axelrad A. A. Improved plasma culture system for production of erythrocytic colonies in vitro: quantitative assay method for CFU-E. Blood. 1974 Oct;44(4):517–534. [PubMed] [Google Scholar]
- Morrison S. J., Hemmati H. D., Wandycz A. M., Weissman I. L. The purification and characterization of fetal liver hematopoietic stem cells. Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10302–10306. doi: 10.1073/pnas.92.22.10302. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Orkin S. H., Harosi F. I., Leder P. Differentiation in erythroleukemic cells and their somatic hybrids. Proc Natl Acad Sci U S A. 1975 Jan;72(1):98–102. doi: 10.1073/pnas.72.1.98. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Palacios R., Imhof B. A. At day 8-8.5 of mouse development the yolk sac, not the embryo proper, has lymphoid precursor potential in vivo and in vitro. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6581–6585. doi: 10.1073/pnas.90.14.6581. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parsons S. F., Mallinson G., Holmes C. H., Houlihan J. M., Simpson K. L., Mawby W. J., Spurr N. K., Warne D., Barclay A. N., Anstee D. J. The Lutheran blood group glycoprotein, another member of the immunoglobulin superfamily, is widely expressed in human tissues and is developmentally regulated in human liver. Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5496–5500. doi: 10.1073/pnas.92.12.5496. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Patel D. D., Haynes B. F. Cell adhesion molecules involved in intrathymic T cell development. Semin Immunol. 1993 Aug;5(4):282–292. doi: 10.1006/smim.1993.1032. [DOI] [PubMed] [Google Scholar]
- Peduzzi J. D., Irwin M. H., Geisert E. E., Jr Distribution and characteristics of a 90 kDa protein, KG-CAM, in the rat CNS. Brain Res. 1994 Mar 21;640(1-2):296–307. doi: 10.1016/0006-8993(94)91885-6. [DOI] [PubMed] [Google Scholar]
- Pelkonen J., Sideras P., Rammensee H. G., Karjalainen K., Palacios R. Thymocyte clones from 14-day mouse embryos. I. State of T cell receptor genes, surface markers, and growth requirements. J Exp Med. 1987 Nov 1;166(5):1245–1258. doi: 10.1084/jem.166.5.1245. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Piali L., Hammel P., Uherek C., Bachmann F., Gisler R. H., Dunon D., Imhof B. A. CD31/PECAM-1 is a ligand for alpha v beta 3 integrin involved in adhesion of leukocytes to endothelium. J Cell Biol. 1995 Jul;130(2):451–460. doi: 10.1083/jcb.130.2.451. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pink J. R., Rijnbeek A. M. Monoclonal antibodies against chicken lymphocyte surface antigens. Hybridoma. 1983;2(3):287–296. doi: 10.1089/hyb.1983.2.287. [DOI] [PubMed] [Google Scholar]
- Pourquié O., Corbel C., Le Caer J. P., Rossier J., Le Douarin N. M. BEN, a surface glycoprotein of the immunoglobulin superfamily, is expressed in a variety of developing systems. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5261–5265. doi: 10.1073/pnas.89.12.5261. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Péault B., Weissman I. L., Baum C., McCune J. M., Tsukamoto A. Lymphoid reconstitution of the human fetal thymus in SCID mice with CD34+ precursor cells. J Exp Med. 1991 Nov 1;174(5):1283–1286. doi: 10.1084/jem.174.5.1283. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Radke K., Beug H., Kornfeld S., Graf T. Transformation of both erythroid and myeloid cells by E26, an avian leukemia virus that contains the myb gene. Cell. 1982 Dec;31(3 Pt 2):643–653. doi: 10.1016/0092-8674(82)90320-8. [DOI] [PubMed] [Google Scholar]
- Ramos R. G., Igloi G. L., Lichte B., Baumann U., Maier D., Schneider T., Brandstätter J. H., Fröhlich A., Fischbach K. F. The irregular chiasm C-roughest locus of Drosophila, which affects axonal projections and programmed cell death, encodes a novel immunoglobulin-like protein. Genes Dev. 1993 Dec;7(12B):2533–2547. doi: 10.1101/gad.7.12b.2533. [DOI] [PubMed] [Google Scholar]
- 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]
- Rodewald H. R., Kretzschmar K., Takeda S., Hohl C., Dessing M. Identification of pro-thymocytes in murine fetal blood: T lineage commitment can precede thymus colonization. EMBO J. 1994 Sep 15;13(18):4229–4240. doi: 10.1002/j.1460-2075.1994.tb06743.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ruiz P., Dunon D., Sonnenberg A., Imhof B. A. Suppression of mouse melanoma metastasis by EA-1, a monoclonal antibody specific for alpha 6 integrins. Cell Adhes Commun. 1993 May;1(1):67–81. [PubMed] [Google Scholar]
- Ruiz P., Wiles M. V., Imhof B. A. Alpha 6 integrins participate in pro-T cell homing to the thymus. Eur J Immunol. 1995 Jul;25(7):2034–2041. doi: 10.1002/eji.1830250735. [DOI] [PubMed] [Google Scholar]
- Savagner P., Imhof B. A., Yamada K. M., Thiery J. P. Homing of hemopoietic precursor cells to the embryonic thymus: characterization of an invasive mechanism induced by chemotactic peptides. J Cell Biol. 1986 Dec;103(6 Pt 2):2715–2727. doi: 10.1083/jcb.103.6.2715. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sers C., Kirsch K., Rothbächer U., Riethmüller G., Johnson J. P. Genomic organization of the melanoma-associated glycoprotein MUC18: implications for the evolution of the immunoglobulin domains. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8514–8518. doi: 10.1073/pnas.90.18.8514. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shyjan A. M., Bertagnolli M., Kenney C. J., Briskin M. J. Human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) demonstrates structural and functional similarities to the alpha 4 beta 7-integrin binding domains of murine MAdCAM-1, but extreme divergence of mucin-like sequences. J Immunol. 1996 Apr 15;156(8):2851–2857. [PubMed] [Google Scholar]
- Steinlein P., Wessely O., Meyer S., Deiner E. M., Hayman M. J., Beug H. Primary, self-renewing erythroid progenitors develop through activation of both tyrosine kinase and steroid hormone receptors. Curr Biol. 1995 Feb 1;5(2):191–204. doi: 10.1016/s0960-9822(95)00040-6. [DOI] [PubMed] [Google Scholar]
- Taira E., Nagino T., Taniura H., Takaha N., Kim C. H., Kuo C. H., Li B. S., Higuchi H., Miki N. Expression and functional analysis of a novel isoform of gicerin, an immunoglobulin superfamily cell adhesion molecule. J Biol Chem. 1995 Dec 1;270(48):28681–28687. doi: 10.1074/jbc.270.48.28681. [DOI] [PubMed] [Google Scholar]
- Taira E., Takaha N., Taniura H., Kim C. H., Miki N. Molecular cloning and functional expression of gicerin, a novel cell adhesion molecule that binds to neurite outgrowth factor. Neuron. 1994 Apr;12(4):861–872. doi: 10.1016/0896-6273(94)90338-7. [DOI] [PubMed] [Google Scholar]
- Takaha N., Taira E., Taniura H., Nagino T., Tsukamoto Y., Matsumoto T., Kotani T., Sakuma S., Miki N. Expression of gicerin in development, oncogenesis and regeneration of the chick kidney. Differentiation. 1995 Jun;58(5):313–320. doi: 10.1046/j.1432-0436.1995.5850313.x. [DOI] [PubMed] [Google Scholar]
- Tamura G. S., Dailey M. O., Gallatin W. M., McGrath M. S., Weissman I. L., Pillemer E. A. Isolation of molecules recognized by monoclonal antibodies and antisera: the solid phase immunoisolation technique. Anal Biochem. 1984 Feb;136(2):458–464. doi: 10.1016/0003-2697(84)90244-6. [DOI] [PubMed] [Google Scholar]
- Tanaka H., Matsui T., Agata A., Tomura M., Kubota I., McFarland K. C., Kohr B., Lee A., Phillips H. S., Shelton D. L. Molecular cloning and expression of a novel adhesion molecule, SC1. Neuron. 1991 Oct;7(4):535–545. doi: 10.1016/0896-6273(91)90366-8. [DOI] [PubMed] [Google Scholar]
- Taussig R., Gilman A. G. Mammalian membrane-bound adenylyl cyclases. J Biol Chem. 1995 Jan 6;270(1):1–4. doi: 10.1074/jbc.270.1.1. [DOI] [PubMed] [Google Scholar]
- Tryggvason K. The laminin family. Curr Opin Cell Biol. 1993 Oct;5(5):877–882. doi: 10.1016/0955-0674(93)90038-r. [DOI] [PubMed] [Google Scholar]
- Yoshida H., Hasegawa S., Kuromi H., Inagaki N., Seino S., Takahashi K., Sato K. A variant form of laminin is responsible for the neurite outgrowth-promoting activity in conditioned medium from a squamous carcinoma cell line. Connect Tissue Res. 1993;30(1):23–35. doi: 10.3109/03008209309032928. [DOI] [PubMed] [Google Scholar]
- Young J. R., Davison T. F., Tregaskes C. A., Rennie M. C., Vainio O. Monomeric homologue of mammalian CD28 is expressed on chicken T cells. J Immunol. 1994 Apr 15;152(8):3848–3851. [PubMed] [Google Scholar]