Skip to main content
Log in

Light and electron microscopic immunolocalization of endothelial leucocyte adhesion molecule-1 in inflammatory bowel disease

Morphological evidence of active synthesis and secretion into vascular lumen

  • Original Articles
  • Published:
Virchows Archiv A Aims and scope Submit manuscript

Summary

Endothelial leucocyte adhesion molecule-1 (ELAM-1) is a rapidly inducible adhesion molecule for neutrophils in vascular endothelial cells. We investigated its immunohistochemical localization in 17 cases of inflammatory bowel disease. ELAM-1 was preferentially expressed in venules in actively inflamed mucosa and granulation tissue. Most capillaries were negative for ELAM-1. In areas with mild inflammation its expression diminished markedly and in normal mucosa of the colon and small intestine its expression was sparse. Electron microscopically, venules in active inflammation had swollen endothelial cells with well-developed rough endoplasmic reticulum. Immunoelectron microscopy revealed ELAM-1 localization along the luminal plasma membrane and in rough endoplasmic reticulum and round granules, findings suggestive of active production in endothelial cells. Furthermore, exocytosis of immuno-reactive substance into the lumen was confirmed. Our study suggests that venules in actively inflamed area play an important role in eliciting and/or maintaining acute inflammatory processes by active permeation of neutrophils from the blood stream into the tissue, and that ELAM-1 may be a secretory protein as well as a transmembrane receptor protein.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Beilke MA (1989) Vascular endothelium in immunology and infectious diseases. Rev Infect Dis 11:273–283

    Google Scholar 

  • Bevilacqua MP, Pober JS, Mendrick DL, Cotran RS, Gimbrone MA Jr (1987) Identification of an inducible endothelial-leukocyte adhesion molecule. Proc Natl Acad Sci USA 84:9238–9242

    Google Scholar 

  • Bevilacqua MP, Stengelin S, Gimbrone MA Jr, Seed B (1989) Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science 243:1160–1165

    Google Scholar 

  • Fukushi Y, Nudelman E, Levery SB, Rauvala H, Hakomori S (1984) Novel fucolipids accumulating in human adenocarcinoma. III. A hybridoma antibody (FH6) defining a human cancer-associated difucoganglioside (VI3NeuAcV3III3Fuc2nLc6). J Biol Chem 259:10511–10517

    Google Scholar 

  • Groves RW, Allen MH, Barker JN, Haskard DO, MacDonald DM (1991) Endothelial leukocyte adhesion molecule-1 (ELAM-1) expression in cutaneous inflammation. Br J Dermatol 124:117–123

    Google Scholar 

  • Isenberg WM, McEver RP, Shuman MA, Bainton DF (1986) Topographic distribution of a granule membrane protein (GMP140) that is expressed on the platelet surface after activation: an immunogold-surface replica study. Blood Cells 12:191–204

    Google Scholar 

  • Johnston GI, Cook RG, McEver RP (1989) Cloning of GMP-140, a granule membrane protein of platelets and endothelium: sequence similarity to proteins involved in cell adhesion and inflammation. Cell 56:1033–1040

    Google Scholar 

  • Koch AE, Burrows JC, Naines GK, Carlos TM, Harlan JM, Leibovich SJ (1991) Immunolocalization of endothelial and leukocyte adhesion molecules in human rheumatoid and osteoarthritic synovial tissues. Lab Invest 64:313–320

    Google Scholar 

  • Lowe JB, Stoolman LM, Nair RP, Larsen RD, Berhend TL, Marks RM (1990) ELAM-1 dependent cell adhesion to vascular endothelium determined by a transfected human fucosyltransferase cDNA. Cell 63:475–484

    Google Scholar 

  • Matis WL, Lavker RM, Murphy GF (1990) Substance P induces the expression of an endothelial-leukocyte adhesion molecule by microvascular endothelium. J Invest Dermatol 94:492–495

    Google Scholar 

  • Matsumoto T, Kitano A, Nakamura S, Oshitani N, Obata A, Hiki M, Hashimura H, Okawa K, Kobayashi K, Nagura H (1989) Possible role of vascular endothelial cells in immune responses in colonic mucosa examined immunocytochemically in subjects with and without ulcerative colitis. Clin Exp Immunol 78:424–430

    Google Scholar 

  • Nakamura S, Ohtani H, Fukushima K, Sasaki I, Matsuno S, Matsumoto T, Kitano A, Kobayashi K, Nagura H (1991) Immunohistochemical study on the distribution of cell adhesion molecules in inflammatory bowel disease (in Japanese). Shokaki to Men'eki (Digest Organ Immunol) 25:110–114

    Google Scholar 

  • Ohtani H, Nagura H (1990) Differing microvasculature in the two major types of gastric carcinoma: a conventional, ultrastructural and ultrastructural immunolocalization study of von Wille-brand factor. Virchows Arch [A] 417:29–35

    Google Scholar 

  • Ohtani H, Sasano N (1983) Stromal cell changes in human colorectal adenomas and carcinomas. An ulrastructural study of fibroblasts, myofibroblasts, and smooth muscle cells. Virchows Arch [A] 401:209–222

    Google Scholar 

  • Ohtani H, Sasano N (1987) Characterization of microvasculature in the stroma of human colorectal carcinoma: an immunoelectron microscopic study on factor VIII/von Willebrand factor. J Electron Microsc 36:204–212

    Google Scholar 

  • Phillips ML, Nudelman E, Gaeta CA, Perez M, Singhai AK, Hakomori S, Paulson JC (1990) ELAM-1 mediates cell adhesion by recognition of a carbohydrate ligand, sialyl-Lex. Science 250:1130–1135

    Google Scholar 

  • Picker LJ, Kishimoto TK, Smith CW, Warnock RA, Butcher EC (1991) ELAM-1 is an adhesion molecule for skin-homing T cells. Nature 349:796–799

    Google Scholar 

  • Pober JS (1988) Cytokine-mediated activation of vascular endothelium. Physiology and pathology. Am J Pathol 133:426–433

    Google Scholar 

  • Redl H, Dinges HP, Buurman WA, Linden CJ van der, Pober JS, Contran RS, Schlag G (1991) Expression of endothelial leukocyte adhesion molecule-1 in septic but not traumatic/hypovolemic shock in the baboon. Am J Pathol 139:461–466

    Google Scholar 

  • Rice GE, Munro JM, Corless C, Bevilacqua (1991) Vascular and nonvascular expression of INCAM-110. A target for mononuclear leukocyte adhesion in normal and inflamed human tissue. Am J Pathol 138:385–393

    Google Scholar 

  • Ruco LP, Pomponi D, Pigott R, Stoppacciaro A, Monardo F, Uccini S, Boraschi D, Tagliabue A, Santoni A, Dejana E, Mantovani A, Baroni CD (1990) Cytokine production (IL-1α, IL-1β, and TNFα) and endothelial cell activation (ELAM-1 and HLA-DR) in reactive lymphadenitis, Hodgkin's disease, and in non-Hodgkin's lymphomas. Am J Pathol 137:1163–1171

    Google Scholar 

  • Shimizu Y, Shaw S, Graber N, Gopal TV, Horgan KJ, Seventer FA van, Newman W (1991) Activation-independent binding of human memory T cells to adhesion molecule ELAM-1. Nature 346:799–802

    Google Scholar 

  • Symington FW, Hedges DL, Hakomori S (1985) Glycolipid antigens of human polymorphonuclear neutrophils and the inducible HL-60 myeloid leukemia line. J Immunol 134:2498–2506

    Google Scholar 

  • Takeuchi M, Nagura H, Kaneda T (1988) DDAVP and epinephrine-induced changes in the localization of von Willebrand factor antigen in endothelial cells of human oral mucosa. Blood 72:850–854

    Google Scholar 

  • Yong K, Khwaja A (1990) Leucocyte cellular adhesion molecules. Blood Rev 4:211–225

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ohtani, H., Nakamura, S., Watanabe, Y. et al. Light and electron microscopic immunolocalization of endothelial leucocyte adhesion molecule-1 in inflammatory bowel disease. Vichows Archiv A Pathol Anat 420, 403–409 (1992). https://doi.org/10.1007/BF01600511

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01600511

Key words

Navigation