Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1991 Jun 2;113(6):1425–1437. doi: 10.1083/jcb.113.6.1425

Identification of a novel high molecular weight protein preferentially expressed by sinusoidal endothelial cells in normal human tissues

PMCID: PMC2289031  PMID: 2045420

Abstract

Mouse mAb MS-1, raised against human spleen, detects an endothelial cell antigen abundantly expressed by the sinusoidal endothelia of spleen, lymph node, liver, and adrenal cortex, but absent from nonsinusoidal continuous endothelia in these organs. Immunoelectron microscopy of splenic tissue demonstrates that the MS-1 antigen is predominantly deposited at zones of intercellular contact between adjacent sinusoidal endothelial cells. mAb MS-1 also reacts with a variable proportion of high endothelial venules in tonsil, but not in other lymphoid tissues, and with an interstitial dendritic cell population most abundant in placenta. mAb MS-1 does not react with cultured resting or mediator- activated human umbilical vein endothelial cells, dermal fibroblasts, peripheral blood mononuclear cells, or the cell lines U937, HL-60, K562 or Mo7E; it does react with the primitive myeloid cell line KG-1. mAb MS-1 immunoprecipitates a major protein of 215 kD and minor proteins of 320 and 120 kD from splenic extracts as analyzed by SDS-PAGE with reduction. These proteins are soluble in aqueous buffers. Immunoprecipitation from KG-1 cell lysates detects four proteins of 280, 300, 205, and 120 kD; the 300-, 205-, and 120-kD species, presumably corresponding to the 320-, 215-, and 120-kD species in spleen, respectively, are secreted into the media. Under nonreducing conditions, immunoprecipitates from KG-1 cell lysates or conditioned media contain one predominant 300-kD species; upon isolation and reduction, this 300-kD species separates into the previously observed 300-, 205-, and 120-kD species. Pulse-chase experiments and limited proteolysis peptide mapping suggest that the 280-kD species is a precursor of the mature 300-kD species which may be subsequently cleaved to yield the 205- and 120-kD species. Because of its size, solubility and expression pattern, the antigen recognized by mAb MS-1 is likely to be an extracellular matrix protein utilized by endothelial cells of contorted, large caliber, or leaky microvessels that lack a well-formed basement membrane.

Full Text

The Full Text of this article is available as a PDF (8.8 MB).

Selected References

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

  1. Abe M., Kufe D. W. Identification of a family of high molecular weight tumor-associated glycoproteins. J Immunol. 1987 Jul 1;139(1):257–261. [PubMed] [Google Scholar]
  2. Alles J. U., Bosslet K. Immunohistochemical and immunochemical characterization of a new endothelial cell-specific antigen. J Histochem Cytochem. 1986 Feb;34(2):209–214. doi: 10.1177/34.2.2418100. [DOI] [PubMed] [Google Scholar]
  3. Aufderheide E., Ekblom P. Tenascin during gut development: appearance in the mesenchyme, shift in molecular forms, and dependence on epithelial-mesenchymal interactions. J Cell Biol. 1988 Dec;107(6 Pt 1):2341–2349. doi: 10.1083/jcb.107.6.2341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Aukhil I., Slemp C. C., Lightner V. A., Nishimura K., Briscoe G., Erickson H. P. Purification of hexabrachion (tenascin) from cell culture conditioned medium, and separation from a cell adhesion factor. Matrix. 1990 May;10(2):98–111. doi: 10.1016/s0934-8832(11)80176-9. [DOI] [PubMed] [Google Scholar]
  5. Beschorner W. E., Civin C. I., Strauss L. C. Localization of hematopoietic progenitor cells in tissue with the anti-My-10 monoclonal antibody. Am J Pathol. 1985 Apr;119(1):1–4. [PMC free article] [PubMed] [Google Scholar]
  6. Bloom A. L., Giddings J. C., Wilks C. J. Factor 8 on the vascular intima: possible importance in haemostasis and thrombosis. Nat New Biol. 1973 Feb 14;241(111):217–219. doi: 10.1038/newbio241217a0. [DOI] [PubMed] [Google Scholar]
  7. Bordier C. Phase separation of integral membrane proteins in Triton X-114 solution. J Biol Chem. 1981 Feb 25;256(4):1604–1607. [PubMed] [Google Scholar]
  8. Bourdon M. A., Wikstrand C. J., Furthmayr H., Matthews T. J., Bigner D. D. Human glioma-mesenchymal extracellular matrix antigen defined by monoclonal antibody. Cancer Res. 1983 Jun;43(6):2796–2805. [PubMed] [Google Scholar]
  9. Buckley P. J., Dickson S. A., Walker W. S. Human splenic sinusoidal lining cells express antigens associated with monocytes, macrophages, endothelial cells, and T lymphocytes. J Immunol. 1985 Apr;134(4):2310–2315. [PubMed] [Google Scholar]
  10. Civin C. I., Strauss L. C., Brovall C., Fackler M. J., Schwartz J. F., Shaper J. H. Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells. J Immunol. 1984 Jul;133(1):157–165. [PubMed] [Google Scholar]
  11. Cleveland D. W., Fischer S. G., Kirschner M. W., Laemmli U. K. Peptide mapping by limited proteolysis in sodium dodecyl sulfate and analysis by gel electrophoresis. J Biol Chem. 1977 Feb 10;252(3):1102–1106. [PubMed] [Google Scholar]
  12. Croghan G. A., Papsidero L. D., Valenzuela L. A., Nemoto T., Penetrante R., Chu T. M. Tissue distribution of an epithelial and tumor-associated antigen recognized by monoclonal antibody F36/22. Cancer Res. 1983 Oct;43(10):4980–4988. [PubMed] [Google Scholar]
  13. Cui Y. C., Tai P. C., Gatter K. C., Mason D. Y., Spry C. J. A vascular endothelial cell antigen with restricted distribution in human foetal, adult and malignant tissues. Immunology. 1983 May;49(1):183–189. [PMC free article] [PubMed] [Google Scholar]
  14. Didinsky J. B., Rheinwald J. G. Failure of hydrocortisone or growth factors to influence the senescence of fibroblasts in a new culture system for assessing replicative lifespan. J Cell Physiol. 1981 Oct;109(1):171–179. doi: 10.1002/jcp.1041090119. [DOI] [PubMed] [Google Scholar]
  15. Drenckhahn D., Wagner J. Stress fibers in the splenic sinus endothelium in situ: molecular structure, relationship to the extracellular matrix, and contractility. J Cell Biol. 1986 May;102(5):1738–1747. doi: 10.1083/jcb.102.5.1738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Duijvestijn A. M., Horst E., Pals S. T., Rouse B. N., Steere A. C., Picker L. J., Meijer C. J., Butcher E. C. High endothelial differentiation in human lymphoid and inflammatory tissues defined by monoclonal antibody HECA-452. Am J Pathol. 1988 Jan;130(1):147–155. [PMC free article] [PubMed] [Google Scholar]
  17. Erickson H. P., Bourdon M. A. Tenascin: an extracellular matrix protein prominent in specialized embryonic tissues and tumors. Annu Rev Cell Biol. 1989;5:71–92. doi: 10.1146/annurev.cb.05.110189.000443. [DOI] [PubMed] [Google Scholar]
  18. Fina L., Molgaard H. V., Robertson D., Bradley N. J., Monaghan P., Delia D., Sutherland D. R., Baker M. A., Greaves M. F. Expression of the CD34 gene in vascular endothelial cells. Blood. 1990 Jun 15;75(12):2417–2426. [PubMed] [Google Scholar]
  19. Gimbrone M. A., Jr Culture of vascular endothelium. Prog Hemost Thromb. 1976;3:1–28. [PubMed] [Google Scholar]
  20. Goerdt S., Steckel F., Schulze-Osthoff K., Hagemeier H. H., Macher E., Sorg C. Characterization and differential expression of an endothelial cell-specific surface antigen in continuous and sinusoidal endothelial, in skin vascular lesions and in vitro. Exp Cell Biol. 1989;57(4):185–192. doi: 10.1159/000163524. [DOI] [PubMed] [Google Scholar]
  21. Groom A. C. The Microcirculatory Society Eugene M. Landis award lecture. Microcirculation of the spleen: new concepts, new challenges. Microvasc Res. 1987 Nov;34(3):269–289. doi: 10.1016/0026-2862(87)90061-6. [DOI] [PubMed] [Google Scholar]
  22. Hagemeier H. H., Vollmer E., Goerdt S., Schulze-Osthoff K., Sorg C. A monoclonal antibody reacting with endothelial cells of budding vessels in tumors and inflammatory tissues, and non-reactive with normal adult tissues. Int J Cancer. 1986 Oct 15;38(4):481–488. doi: 10.1002/ijc.2910380405. [DOI] [PubMed] [Google Scholar]
  23. Heimark R. L., Degner M., Schwartz S. M. Identification of a Ca2(+)-dependent cell-cell adhesion molecule in endothelial cells. J Cell Biol. 1990 May;110(5):1745–1756. doi: 10.1083/jcb.110.5.1745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Jefferies W. A., Brandon M. R., Hunt S. V., Williams A. F., Gatter K. C., Mason D. Y. Transferrin receptor on endothelium of brain capillaries. Nature. 1984 Nov 8;312(5990):162–163. doi: 10.1038/312162a0. [DOI] [PubMed] [Google Scholar]
  25. King J. T., Puchtler H., Sweat F. Ring fibers in human spleens. Arch Pathol. 1968 Mar;85(3):237–245. [PubMed] [Google Scholar]
  26. Knowles D. M., 2nd, Tolidjian B., Marboe C., D'Agati V., Grimes M., Chess L. Monoclonal anti-human monocyte antibodies OKM1 and OKM5 possess distinctive tissue distributions including differential reactivity with vascular endothelium. J Immunol. 1984 May;132(5):2170–2173. [PubMed] [Google Scholar]
  27. Ledger P. W., Nishimoto S. K., Hayashi S., Tanzer M. L. Abnormal glycosylation of human fibronectin secreted in the presence of monensin. J Biol Chem. 1983 Jan 10;258(1):547–554. [PubMed] [Google Scholar]
  28. Lightner V. A., Gumkowski F., Bigner D. D., Erickson H. P. Tenascin/hexabrachion in human skin: biochemical identification and localization by light and electron microscopy. J Cell Biol. 1989 Jun;108(6):2483–2493. doi: 10.1083/jcb.108.6.2483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. MacDonald I. C., Ragan D. M., Schmidt E. E., Groom A. C. Kinetics of red blood cell passage through interendothelial slits into venous sinuses in rat spleen, analyzed by in vivo microscopy. Microvasc Res. 1987 Jan;33(1):118–134. doi: 10.1016/0026-2862(87)90011-2. [DOI] [PubMed] [Google Scholar]
  30. Meloan S. N., Waldrop F. S., Puchtler H., Valentine L. S. Cross-striated myoendothelial cells in splenic venous sinuses. J Reticuloendothel Soc. 1972 Jun;11(6):566–578. [PubMed] [Google Scholar]
  31. Mues B., Langer D., Zwadlo G., Sorg C. Phenotypic characterization of macrophages in human term placenta. Immunology. 1989 Jul;67(3):303–307. [PMC free article] [PubMed] [Google Scholar]
  32. Muller W. A., Ratti C. M., McDonnell S. L., Cohn Z. A. A human endothelial cell-restricted, externally disposed plasmalemmal protein enriched in intercellular junctions. J Exp Med. 1989 Aug 1;170(2):399–414. doi: 10.1084/jem.170.2.399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Newman P. J., Berndt M. C., Gorski J., White G. C., 2nd, Lyman S., Paddock C., Muller W. A. PECAM-1 (CD31) cloning and relation to adhesion molecules of the immunoglobulin gene superfamily. Science. 1990 Mar 9;247(4947):1219–1222. doi: 10.1126/science.1690453. [DOI] [PubMed] [Google Scholar]
  34. Nickoloff B. J., Griffiths C. E. Factor XIIIa-expressing dermal dendrocytes in AIDS-associated cutaneous Kaposi's sarcomas. Science. 1989 Mar 31;243(4899):1736–1737. doi: 10.1126/science.2564703. [DOI] [PubMed] [Google Scholar]
  35. Peters J. H., Sporn L. A., Ginsberg M. H., Wagner D. D. Human endothelial cells synthesize, process, and secrete fibronectin molecules bearing an alternatively spliced type III homology (ED1). Blood. 1990 May 1;75(9):1801–1808. [PubMed] [Google Scholar]
  36. Pinkus G. S., Warhol M. J., O'Connor E. M., Etheridge C. L., Fujiwara K. Immunohistochemical localization of smooth muscle myosin in human spleen, lymph node, and other lymphoid tissues. Unique staining patterns in splenic white pulp and sinuses, lymphoid follicles, and certain vasculature, with ultrastructural correlations. Am J Pathol. 1986 Jun;123(3):440–453. [PMC free article] [PubMed] [Google Scholar]
  37. Pober J. S., Gimbrone M. A., Jr, Lapierre L. A., Mendrick D. L., Fiers W., Rothlein R., Springer T. A. Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. J Immunol. 1986 Sep 15;137(6):1893–1896. [PubMed] [Google Scholar]
  38. Posnett D. N., Marboe C. C., Knowles D. M., 2nd, Jaffe E. A., Kunkel H. G. A membrane antigen (HC1) selectively present on hairy cell leukemia cells, endothelial cells, and epidermal basal cells. J Immunol. 1984 Jun;132(6):2700–2702. [PubMed] [Google Scholar]
  39. SNOOK T. A comparative study of the vascular arrangements in mammalian spleens. Am J Anat. 1950 Jul;87(1):31–77. doi: 10.1002/aja.1000870103. [DOI] [PubMed] [Google Scholar]
  40. Schlingemann R. O., Dingjan G. M., Emeis J. J., Blok J., Warnaar S. O., Ruiter D. J. Monoclonal antibody PAL-E specific for endothelium. Lab Invest. 1985 Jan;52(1):71–76. [PubMed] [Google Scholar]
  41. Schlingemann R. O., Rietveld F. J., de Waal R. M., Bradley N. J., Skene A. I., Davies A. J., Greaves M. F., Denekamp J., Ruiter D. J. Leukocyte antigen CD34 is expressed by a subset of cultured endothelial cells and on endothelial abluminal microprocesses in the tumor stroma. Lab Invest. 1990 Jun;62(6):690–696. [PubMed] [Google Scholar]
  42. Schmidt E. E., MacDonald I. C., Groom A. C. Circulatory pathways in the sinusal spleen of the dog, studied by scanning electron microscopy of microcorrosion casts. J Morphol. 1983 Nov;178(2):111–123. doi: 10.1002/jmor.1051780204. [DOI] [PubMed] [Google Scholar]
  43. Schmidt E. E., MacDonald I. C., Groom A. C. The intermediate circulation in the nonsinusal spleen of the cat, studied by scanning electron microscopy of microcorrosion casts. J Morphol. 1983 Nov;178(2):125–138. doi: 10.1002/jmor.1051780205. [DOI] [PubMed] [Google Scholar]
  44. Scully P. A., Steinman H. K., Kennedy C., Trueblood K., Frisman D. M., Voland J. R. AIDS-related Kaposi's sarcoma displays differential expression of endothelial surface antigens. Am J Pathol. 1988 Feb;130(2):244–251. [PMC free article] [PubMed] [Google Scholar]
  45. Spencer S. C., Fabre J. W. Characterization of the tissue macrophage and the interstitial dendritic cell as distinct leukocytes normally resident in the connective tissue of rat heart. J Exp Med. 1990 Jun 1;171(6):1841–1851. doi: 10.1084/jem.171.6.1841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Thornton S. C., Mueller S. N., Levine E. M. Human endothelial cells: use of heparin in cloning and long-term serial cultivation. Science. 1983 Nov 11;222(4624):623–625. doi: 10.1126/science.6635659. [DOI] [PubMed] [Google Scholar]
  47. Turner R. R., Beckstead J. H., Warnke R. A., Wood G. S. Endothelial cell phenotypic diversity. In situ demonstration of immunologic and enzymatic heterogeneity that correlates with specific morphologic subtypes. Am J Clin Pathol. 1987 May;87(5):569–575. doi: 10.1093/ajcp/87.5.569. [DOI] [PubMed] [Google Scholar]
  48. Vartio T., Laitinen L., Närvänen O., Cutolo M., Thornell L. E., Zardi L., Virtanen I. Differential expression of the ED sequence-containing form of cellular fibronectin in embryonic and adult human tissues. J Cell Sci. 1987 Nov;88(Pt 4):419–430. doi: 10.1242/jcs.88.4.419. [DOI] [PubMed] [Google Scholar]
  49. Wacker H. H., Radzun H. J., Mielke V., Parwaresch M. R. Selective recognition of rat follicular dendritic cells (dendritic reticulum cells) by a new monoclonal antibody Ki-M4R in vitro and in vivo. J Leukoc Biol. 1987 Jan;41(1):70–77. doi: 10.1002/jlb.41.1.70. [DOI] [PubMed] [Google Scholar]
  50. Wagner D. D., Marder V. J. Biosynthesis of von Willebrand protein by human endothelial cells: processing steps and their intracellular localization. J Cell Biol. 1984 Dec;99(6):2123–2130. doi: 10.1083/jcb.99.6.2123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Wion K. L., Kelly D., Summerfield J. A., Tuddenham E. G., Lawn R. M. Distribution of factor VIII mRNA and antigen in human liver and other tissues. Nature. 1985 Oct 24;317(6039):726–729. doi: 10.1038/317726a0. [DOI] [PubMed] [Google Scholar]

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

RESOURCES