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. 1994 May;144(5):952–961.

Increase in the adhesion molecule P-selectin in endothelium overlying atherosclerotic plaques. Coexpression with intercellular adhesion molecule-1.

R R Johnson-Tidey 1, J L McGregor 1, P R Taylor 1, R N Poston 1
PMCID: PMC1887356  PMID: 7513951

Abstract

P-selectin (GMP-140) is an adhesion molecule present within endothelial cells that is rapidly translocated to the cell membrane upon activation, where it mediates endothelial-leukocyte interactions. Immunohistochemical analysis of human atherosclerotic plaques has shown strong expression of P-selectin by the endothelium overlying active atherosclerotic plaques. P-selectin is not, however, detected in normal arterial endothelium or in endothelium overlying inactive fibrous plaques. Color image analysis was used to quantitate the degree of P-selectin expression in the endothelium and demonstrates a statistically significant increase in P-selectin expression by atherosclerotic endothelial cells. Double immunofluorescence shows that some of this P-selectin is expressed on the luminal surface of the endothelial cells. Previous work has demonstrated a significant up-regulation in the expression of the intercellular adhesion molecule-1 in atherosclerotic endothelium and a study on the expression of intercellular adhesion molecule-1 and P-selectin in atherosclerosis shows a highly positive correlation. These results suggest that the selective and cooperative expression of P-selectin and intercellular adhesion molecule-1 may be involved in the recruitment of monocytes into sites of atherosclerosis.

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Selected References

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  1. Andrew S. M., Jasani B. An improved method for the inhibition of endogenous peroxidase non-deleterious to lymphocyte surface markers. Application to immunoperoxidase studies on eosinophil-rich tissue preparations. Histochem J. 1987 Aug;19(8):426–430. doi: 10.1007/BF01675753. [DOI] [PubMed] [Google Scholar]
  2. Aruffo A., Kolanus W., Walz G., Fredman P., Seed B. CD62/P-selectin recognition of myeloid and tumor cell sulfatides. Cell. 1991 Oct 4;67(1):35–44. doi: 10.1016/0092-8674(91)90570-o. [DOI] [PubMed] [Google Scholar]
  3. Bonfanti R., Furie B. C., Furie B., Wagner D. D. PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells. Blood. 1989 Apr;73(5):1109–1112. [PubMed] [Google Scholar]
  4. Cybulsky M. I., Gimbrone M. A., Jr Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science. 1991 Feb 15;251(4995):788–791. doi: 10.1126/science.1990440. [DOI] [PubMed] [Google Scholar]
  5. Faggiotto A., Ross R., Harker L. Studies of hypercholesterolemia in the nonhuman primate. I. Changes that lead to fatty streak formation. Arteriosclerosis. 1984 Jul-Aug;4(4):323–340. doi: 10.1161/01.atv.4.4.323. [DOI] [PubMed] [Google Scholar]
  6. Geng J. G., Bevilacqua M. P., Moore K. L., McIntyre T. M., Prescott S. M., Kim J. M., Bliss G. A., Zimmerman G. A., McEver R. P. Rapid neutrophil adhesion to activated endothelium mediated by GMP-140. Nature. 1990 Feb 22;343(6260):757–760. doi: 10.1038/343757a0. [DOI] [PubMed] [Google Scholar]
  7. Gown A. M., Tsukada T., Ross R. Human atherosclerosis. II. Immunocytochemical analysis of the cellular composition of human atherosclerotic lesions. Am J Pathol. 1986 Oct;125(1):191–207. [PMC free article] [PubMed] [Google Scholar]
  8. Hamburger S. A., McEver R. P. GMP-140 mediates adhesion of stimulated platelets to neutrophils. Blood. 1990 Feb 1;75(3):550–554. [PubMed] [Google Scholar]
  9. Hansson G. K., Jonasson L., Seifert P. S., Stemme S. Immune mechanisms in atherosclerosis. Arteriosclerosis. 1989 Sep-Oct;9(5):567–578. doi: 10.1161/01.atv.9.5.567. [DOI] [PubMed] [Google Scholar]
  10. Hattori R., Hamilton K. K., Fugate R. D., McEver R. P., Sims P. J. Stimulated secretion of endothelial von Willebrand factor is accompanied by rapid redistribution to the cell surface of the intracellular granule membrane protein GMP-140. J Biol Chem. 1989 May 15;264(14):7768–7771. [PubMed] [Google Scholar]
  11. Johnston G. I., Cook R. G., McEver R. P. Cloning of GMP-140, a granule membrane protein of platelets and endothelium: sequence similarity to proteins involved in cell adhesion and inflammation. Cell. 1989 Mar 24;56(6):1033–1044. doi: 10.1016/0092-8674(89)90636-3. [DOI] [PubMed] [Google Scholar]
  12. Larsen E., Celi A., Gilbert G. E., Furie B. C., Erban J. K., Bonfanti R., Wagner D. D., Furie B. PADGEM protein: a receptor that mediates the interaction of activated platelets with neutrophils and monocytes. Cell. 1989 Oct 20;59(2):305–312. doi: 10.1016/0092-8674(89)90292-4. [DOI] [PubMed] [Google Scholar]
  13. Larsen E., Palabrica T., Sajer S., Gilbert G. E., Wagner D. D., Furie B. C., Furie B. PADGEM-dependent adhesion of platelets to monocytes and neutrophils is mediated by a lineage-specific carbohydrate, LNF III (CD15). Cell. 1990 Nov 2;63(3):467–474. doi: 10.1016/0092-8674(90)90443-i. [DOI] [PubMed] [Google Scholar]
  14. Lawrence M. B., Springer T. A. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell. 1991 May 31;65(5):859–873. doi: 10.1016/0092-8674(91)90393-d. [DOI] [PubMed] [Google Scholar]
  15. Lorant D. E., Patel K. D., McIntyre T. M., McEver R. P., Prescott S. M., Zimmerman G. A. Coexpression of GMP-140 and PAF by endothelium stimulated by histamine or thrombin: a juxtacrine system for adhesion and activation of neutrophils. J Cell Biol. 1991 Oct;115(1):223–234. doi: 10.1083/jcb.115.1.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McEver R. P., Beckstead J. H., Moore K. L., Marshall-Carlson L., Bainton D. F. GMP-140, a platelet alpha-granule membrane protein, is also synthesized by vascular endothelial cells and is localized in Weibel-Palade bodies. J Clin Invest. 1989 Jul;84(1):92–99. doi: 10.1172/JCI114175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Miyazaki A., Mirakian R., Bottazzo G. F. Adhesion molecule expression in Graves' thyroid glands; potential relevance of granule membrane protein (GMP-140) and intercellular adhesion molecule-1 (ICAM-1) in the homing and antigen presentation processes. Clin Exp Immunol. 1992 Jul;89(1):52–57. doi: 10.1111/j.1365-2249.1992.tb06876.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Moore K. L., Thompson L. F. P-selectin (CD62) binds to subpopulations of human memory T lymphocytes and natural killer cells. Biochem Biophys Res Commun. 1992 Jul 15;186(1):173–181. doi: 10.1016/s0006-291x(05)80790-9. [DOI] [PubMed] [Google Scholar]
  19. Munro J. M., Cotran R. S. The pathogenesis of atherosclerosis: atherogenesis and inflammation. Lab Invest. 1988 Mar;58(3):249–261. [PubMed] [Google Scholar]
  20. Munro J. M., Pober J. S., Cotran R. S. Tumor necrosis factor and interferon-gamma induce distinct patterns of endothelial activation and associated leukocyte accumulation in skin of Papio anubis. Am J Pathol. 1989 Jul;135(1):121–133. [PMC free article] [PubMed] [Google Scholar]
  21. O'Brien K. D., Allen M. D., McDonald T. O., Chait A., Harlan J. M., Fishbein D., McCarty J., Ferguson M., Hudkins K., Benjamin C. D. Vascular cell adhesion molecule-1 is expressed in human coronary atherosclerotic plaques. Implications for the mode of progression of advanced coronary atherosclerosis. J Clin Invest. 1993 Aug;92(2):945–951. doi: 10.1172/JCI116670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pallesen G., Knudsen L. M. Leucocyte antigens in human post mortem tissues: their preservation and loss as demonstrated by monoclonal antibody immunohistological staining. Histopathology. 1985 Aug;9(8):791–804. doi: 10.1111/j.1365-2559.1985.tb02867.x. [DOI] [PubMed] [Google Scholar]
  23. Parmentier S., McGregor L., Catimel B., Leung L. L., McGregor J. L. Inhibition of platelet functions by a monoclonal antibody (LYP20) directed against a granule membrane glycoprotein (GMP-140/PADGEM). Blood. 1991 Apr 15;77(8):1734–1739. [PubMed] [Google Scholar]
  24. Patel K. D., Zimmerman G. A., Prescott S. M., McEver R. P., McIntyre T. M. Oxygen radicals induce human endothelial cells to express GMP-140 and bind neutrophils. J Cell Biol. 1991 Feb;112(4):749–759. doi: 10.1083/jcb.112.4.749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Picker L. J., Warnock R. A., Burns A. R., Doerschuk C. M., Berg E. L., Butcher E. C. The neutrophil selectin LECAM-1 presents carbohydrate ligands to the vascular selectins ELAM-1 and GMP-140. Cell. 1991 Sep 6;66(5):921–933. doi: 10.1016/0092-8674(91)90438-5. [DOI] [PubMed] [Google Scholar]
  26. Poston R. N., Haskard D. O., Coucher J. R., Gall N. P., Johnson-Tidey R. R. Expression of intercellular adhesion molecule-1 in atherosclerotic plaques. Am J Pathol. 1992 Mar;140(3):665–673. [PMC free article] [PubMed] [Google Scholar]
  27. Skinner M. P., Lucas C. M., Burns G. F., Chesterman C. N., Berndt M. C. GMP-140 binding to neutrophils is inhibited by sulfated glycans. J Biol Chem. 1991 Mar 25;266(9):5371–5374. [PubMed] [Google Scholar]
  28. Spertini O., Luscinskas F. W., Gimbrone M. A., Jr, Tedder T. F. Monocyte attachment to activated human vascular endothelium in vitro is mediated by leukocyte adhesion molecule-1 (L-selectin) under nonstatic conditions. J Exp Med. 1992 Jun 1;175(6):1789–1792. doi: 10.1084/jem.175.6.1789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sugama Y., Tiruppathi C., offakidevi K., Andersen T. T., Fenton J. W., 2nd, Malik A. B. Thrombin-induced expression of endothelial P-selectin and intercellular adhesion molecule-1: a mechanism for stabilizing neutrophil adhesion. J Cell Biol. 1992 Nov;119(4):935–944. doi: 10.1083/jcb.119.4.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tipping P. G., Hancock W. W. Production of tumor necrosis factor and interleukin-1 by macrophages from human atheromatous plaques. Am J Pathol. 1993 Jun;142(6):1721–1728. [PMC free article] [PubMed] [Google Scholar]
  31. Weller A., Isenmann S., Vestweber D. Cloning of the mouse endothelial selectins. Expression of both E- and P-selectin is inducible by tumor necrosis factor alpha. J Biol Chem. 1992 Jul 25;267(21):15176–15183. [PubMed] [Google Scholar]
  32. Wood K. M., Cadogan M. D., Ramshaw A. L., Parums D. V. The distribution of adhesion molecules in human atherosclerosis. Histopathology. 1993 May;22(5):437–444. doi: 10.1111/j.1365-2559.1993.tb00157.x. [DOI] [PubMed] [Google Scholar]
  33. Zhou Q., Moore K. L., Smith D. F., Varki A., McEver R. P., Cummings R. D. The selectin GMP-140 binds to sialylated, fucosylated lactosaminoglycans on both myeloid and nonmyeloid cells. J Cell Biol. 1991 Oct;115(2):557–564. doi: 10.1083/jcb.115.2.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. de Bruijne-Admiraal L. G., Modderman P. W., Von dem Borne A. E., Sonnenberg A. P-selectin mediates Ca(2+)-dependent adhesion of activated platelets to many different types of leukocytes: detection by flow cytometry. Blood. 1992 Jul 1;80(1):134–142. [PubMed] [Google Scholar]
  35. van der Wal A. C., Das P. K., Tigges A. J., Becker A. E. Adhesion molecules on the endothelium and mononuclear cells in human atherosclerotic lesions. Am J Pathol. 1992 Dec;141(6):1427–1433. [PMC free article] [PubMed] [Google Scholar]
  36. von Andrian U. H., Chambers J. D., McEvoy L. M., Bargatze R. F., Arfors K. E., Butcher E. C. Two-step model of leukocyte-endothelial cell interaction in inflammation: distinct roles for LECAM-1 and the leukocyte beta 2 integrins in vivo. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7538–7542. doi: 10.1073/pnas.88.17.7538. [DOI] [PMC free article] [PubMed] [Google Scholar]

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