Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1993 Feb;142(2):579–591.

Expression of vascular cell adhesion molecule (VCAM-1) in liver and pancreas allograft rejection.

C E Bacchi 1, C L Marsh 1, J D Perkins 1, R L Carithers Jr 1, J P McVicar 1, K L Hudkins 1, C D Benjamin 1, J M Harlan 1, R Lobb 1, C E Alpers 1
PMCID: PMC1886742  PMID: 7679554

Abstract

VCAM-1, a leukocyte adhesion molecule expressed by cytokine-activated endothelial cells in culture, may mediate mononuclear leukocyte infiltration in vessels and interstitium in solid organ allograft rejection. Using the avidin-biotin immunoperoxidase technique and two different antibodies--4B9, a murine monoclonal antibody, and rabbit polyclonal antisera to recombinant human VCAM (rVCAM Ab), which work in methacarn-fixed tissues--we studied the expression of this molecule in biopsies of transplanted liver and pancreas with and without features of rejection as well as nontransplant control tissues. The rVCAM Ab, but not 4B9, showed a population of reactive endothelial cells limited to sites of prominent subendothelial leukocytic cell infiltration in arteries and veins in rejecting allografts. VCAM-1 expression by sinusoidal endothelium in rejecting liver allografts was also observed. In addition, a population of cells (DC) with dendritic morphology was identified by rVCAM Ab within sites of lymphoid cell aggregations in both liver and pancreas allografts. Further evidence that these cells represent true DC was obtained by identification of VCAM-1 positive morphologically similar cells in both germinal centers and interfollicular areas of reactive lymph nodes; and by similar staining of these cells in allograft organs by a monoclonal antibody to nerve growth factor receptor, previously shown to recognize DC. DCs were generally not seen in normal control organs or portions of allografts uninvolved by lymphoid aggregates. This study provides evidence that 1) endothelial cell expression of VCAM-1 may be important in transplant rejection, 2) different epitopes of VCAM-1 may be preserved in tissue sections and recognized by different antibodies, and 3) there is probably a population of VCAM-1 expressing DC that participates in the cellular rejection progress.

Full text

PDF
579

Images in this article

582Figure 1
on p.582
584Figure 2
on p.584
585Figure 3
on p.585

Selected References

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

  1. Adams D. H., Hubscher S. G., Shaw J., Rothlein R., Neuberger J. M. Intercellular adhesion molecule 1 on liver allografts during rejection. Lancet. 1989 Nov 11;2(8672):1122–1125. doi: 10.1016/s0140-6736(89)91489-x. [DOI] [PubMed] [Google Scholar]
  2. Alpers C. E., Gordon D., Gown A. M. Immunophenotype of vascular rejection in renal transplants. Mod Pathol. 1990 Mar;3(2):198–203. [PubMed] [Google Scholar]
  3. Bevilacqua M. P., Pober J. S., Mendrick D. L., Cotran R. S., Gimbrone M. A., Jr Identification of an inducible endothelial-leukocyte adhesion molecule. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9238–9242. doi: 10.1073/pnas.84.24.9238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bevilacqua M. P., Stengelin S., Gimbrone M. A., Jr, Seed B. Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science. 1989 Mar 3;243(4895):1160–1165. doi: 10.1126/science.2466335. [DOI] [PubMed] [Google Scholar]
  5. Bishop G. A., Hall B. M. Expression of leucocyte and lymphocyte adhesion molecules in the human kidney. Kidney Int. 1989 Dec;36(6):1078–1085. doi: 10.1038/ki.1989.303. [DOI] [PubMed] [Google Scholar]
  6. Bishop G. A., Waugh J. A., Landers D. V., Krensky A. M., Hall B. M. Microvascular destruction in renal transplant rejection. Transplantation. 1989 Sep;48(3):408–414. doi: 10.1097/00007890-198909000-00011. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Burkly L. C., Jakubowski A., Newman B. M., Rosa M. D., Chi-Rosso G., Lobb R. R. Signaling by vascular cell adhesion molecule-1 (VCAM-1) through VLA-4 promotes CD3-dependent T cell proliferation. Eur J Immunol. 1991 Nov;21(11):2871–2875. doi: 10.1002/eji.1830211132. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Carlos T., Gordon D., Fishbein D., Himes V. E., Coday A., Ross R., Allen M. D. Vascular cell adhesion molecule-1 is induced on endothelium during acute rejection in human cardiac allografts. J Heart Lung Transplant. 1992 Nov-Dec;11(6):1103–1109. [PubMed] [Google Scholar]
  11. Carlos T., Kovach N., Schwartz B., Rosa M., Newman B., Wayner E., Benjamin C., Osborn L., Lobb R., Harlan J. Human monocytes bind to two cytokine-induced adhesive ligands on cultured human endothelial cells: endothelial-leukocyte adhesion molecule-1 and vascular cell adhesion molecule-1. Blood. 1991 May 15;77(10):2266–2271. [PubMed] [Google Scholar]
  12. Carpenter H. A., Engen D. E., Munn S. R., Barr D., Marsh C. L., Ludwig J., Perkins J. D. Histologic diagnosis of rejection by using cystoscopically directed needle biopsy specimens from dysfunctional pancreatoduodenal allografts with exocrine drainage into the bladder. Am J Surg Pathol. 1990 Sep;14(9):837–846. [PubMed] [Google Scholar]
  13. Clark E. A., Grabstein K. H., Shu G. L. Cultured human follicular dendritic cells. Growth characteristics and interactions with B lymphocytes. J Immunol. 1992 Jun 1;148(11):3327–3335. [PubMed] [Google Scholar]
  14. Cosimi A. B., Conti D., Delmonico F. L., Preffer F. I., Wee S. L., Rothlein R., Faanes R., Colvin R. B. In vivo effects of monoclonal antibody to ICAM-1 (CD54) in nonhuman primates with renal allografts. J Immunol. 1990 Jun 15;144(12):4604–4612. [PubMed] [Google Scholar]
  15. Cybulsky M. I., Fries J. W., Williams A. J., Sultan P., Davis V. M., Gimbrone M. A., Jr, Collins T. Alternative splicing of human VCAM-1 in activated vascular endothelium. Am J Pathol. 1991 Apr;138(4):815–820. [PMC free article] [PubMed] [Google Scholar]
  16. Damle N. K., Aruffo A. Vascular cell adhesion molecule 1 induces T-cell antigen receptor-dependent activation of CD4+T lymphocytes. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6403–6407. doi: 10.1073/pnas.88.15.6403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Demetris A. J., Lasky S., Van Thiel D. H., Starzl T. E., Dekker A. Pathology of hepatic transplantation: A review of 62 adult allograft recipients immunosuppressed with a cyclosporine/steroid regimen. Am J Pathol. 1985 Jan;118(1):151–161. [PMC free article] [PubMed] [Google Scholar]
  18. Demetris A. J., Qian S. G., Sun H., Fung J. J. Liver allograft rejection: an overview of morphologic findings. Am J Surg Pathol. 1990;14 (Suppl 1):49–63. [PubMed] [Google Scholar]
  19. Demetris A. J., Qian S., Sun H., Fung J. J., Yagihashi A., Murase N., Iwaki Y., Gambrell B., Starzl T. E. Early events in liver allograft rejection. Delineation of sites of simultaneous intragraft and recipient lymphoid tissue sensitization. Am J Pathol. 1991 Mar;138(3):609–618. [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. Gown A. M., Vogel A. M. Monoclonal antibodies to human intermediate filament proteins. II. Distribution of filament proteins in normal human tissues. Am J Pathol. 1984 Feb;114(2):309–321. [PMC free article] [PubMed] [Google Scholar]
  23. Hruban R. H., Beschorner W. E., Baumgartner W. A., Augustine S. M., Ren H., Reitz B. A., Hutchins G. M. Accelerated arteriosclerosis in heart transplant recipients is associated with a T-lymphocyte-mediated endothelialitis. Am J Pathol. 1990 Oct;137(4):871–882. [PMC free article] [PubMed] [Google Scholar]
  24. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  25. Hubscher S. G. Histological findings in liver allograft rejection--new insights into the pathogenesis of hepatocellular damage in liver allografts. Histopathology. 1991 Apr;18(4):377–383. doi: 10.1111/j.1365-2559.1991.tb00865.x. [DOI] [PubMed] [Google Scholar]
  26. Isobe M., Yagita H., Okumura K., Ihara A. Specific acceptance of cardiac allograft after treatment with antibodies to ICAM-1 and LFA-1. Science. 1992 Feb 28;255(5048):1125–1127. doi: 10.1126/science.1347662. [DOI] [PubMed] [Google Scholar]
  27. Johnson R. J., Garcia R. L., Pritzl P., Alpers C. E. Platelets mediate glomerular cell proliferation in immune complex nephritis induced by anti-mesangial cell antibodies in the rat. Am J Pathol. 1990 Feb;136(2):369–374. [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. Larsen C. P., Morris P. J., Austyn J. M. Migration of dendritic leukocytes from cardiac allografts into host spleens. A novel pathway for initiation of rejection. J Exp Med. 1990 Jan 1;171(1):307–314. doi: 10.1084/jem.171.1.307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lobb R., Chi-Rosso G., Leone D., Rosa M., Newman B., Luhowskyj S., Osborn L., Schiffer S., Benjamin C., Dougas I. Expression and functional characterization of a soluble form of vascular cell adhesion molecule 1. Biochem Biophys Res Commun. 1991 Aug 15;178(3):1498–1504. doi: 10.1016/0006-291x(91)91063-i. [DOI] [PubMed] [Google Scholar]
  31. Ludwig J., Batts K. P., Ploch M., Rakela J., Perkins J. D., Wiesner R. H. Endotheliitis in hepatic allografts. Mayo Clin Proc. 1989 May;64(5):545–554. doi: 10.1016/s0025-6196(12)65560-8. [DOI] [PubMed] [Google Scholar]
  32. Mason D. Y., Comans-Bitter W. M., Cordell J. L., Verhoeven M. A., van Dongen J. J. Antibody L26 recognizes an intracellular epitope on the B-cell-associated CD20 antigen. Am J Pathol. 1990 Jun;136(6):1215–1222. [PMC free article] [PubMed] [Google Scholar]
  33. Norton A. J., Isaacson P. G. Monoclonal antibody L26: an antibody that is reactive with normal and neoplastic B lymphocytes in routinely fixed and paraffin wax embedded tissues. J Clin Pathol. 1987 Dec;40(12):1405–1412. doi: 10.1136/jcp.40.12.1405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Oguma S., Zerbe T., Banner B., Belle S., Starzl T. E., Demetris A. J. Chronic liver allograft rejection and obliterative arteriopathy: possible pathogenic mechanisms. Transplant Proc. 1989 Feb;21(1 Pt 2):2203–2207. [PMC free article] [PubMed] [Google Scholar]
  35. Orosz C. G., van Buskirk A., Sedmak D. D., Kincade P., Miyake K., Pelletier R. P. Role of the endothelial adhesion molecule VCAM in murine cardiac allograft rejection. Immunol Lett. 1992 Mar;32(1):7–12. doi: 10.1016/0165-2478(92)90191-p. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. Renkonen R., Turunen J. P., Rapola J., Häyry P. Characterization of high endothelial-like properties of peritubular capillary endothelium during acute renal allograft rejection. Am J Pathol. 1990 Sep;137(3):643–651. [PMC free article] [PubMed] [Google Scholar]
  38. 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]
  39. Said J. W., Stoll P. N., Shintaku P., Bindl J. M., Butmarc J. R., Pinkus G. S. Leu-22: a preferential marker for T-lymphocytes in paraffin sections. Staining profile in T- and B-cell lymphomas, Hodgkin's disease, other lymphoproliferative disorders, myeloproliferative diseases, and various neoplastic processes. Am J Clin Pathol. 1989 May;91(5):542–549. doi: 10.1093/ajcp/91.5.542. [DOI] [PubMed] [Google Scholar]
  40. Sankary H., Foster P., Hart M., Ashmann M., Schwartz D., Williams J. W. An analysis of the determinants of hepatic allograft rejection using stepwise logistic regression. Transplantation. 1989 Jan;47(1):74–77. doi: 10.1097/00007890-198901000-00017. [DOI] [PubMed] [Google Scholar]
  41. Sibley R. K., Sutherland D. E. Pancreas transplantation. An immunohistologic and histopathologic examination of 100 grafts. Am J Pathol. 1987 Jul;128(1):151–170. [PMC free article] [PubMed] [Google Scholar]
  42. Simmons D., Makgoba M. W., Seed B. ICAM, an adhesion ligand of LFA-1, is homologous to the neural cell adhesion molecule NCAM. Nature. 1988 Feb 18;331(6157):624–627. doi: 10.1038/331624a0. [DOI] [PubMed] [Google Scholar]
  43. Staunton D. E., Dustin M. L., Springer T. A. Functional cloning of ICAM-2, a cell adhesion ligand for LFA-1 homologous to ICAM-1. Nature. 1989 May 4;339(6219):61–64. doi: 10.1038/339061a0. [DOI] [PubMed] [Google Scholar]
  44. Staunton D. E., Marlin S. D., Stratowa C., Dustin M. L., Springer T. A. Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families. Cell. 1988 Mar 25;52(6):925–933. doi: 10.1016/0092-8674(88)90434-5. [DOI] [PubMed] [Google Scholar]
  45. Steinhoff G., Behrend M., Pichlmayr R. Induction of ICAM-1 on hepatocyte membranes during liver allograft rejection and infection. Transplant Proc. 1990 Oct;22(5):2308–2309. [PubMed] [Google Scholar]
  46. Steiniger B., Klempnauer J., Wonigeit K. Phenotype and histological distribution of interstitial dendritic cells in the rat pancreas, liver, heart, and kidney. Transplantation. 1984 Aug;38(2):169–174. doi: 10.1097/00007890-198408000-00016. [DOI] [PubMed] [Google Scholar]
  47. Strobach R. S., Nakamine H., Masih A. S., Linder J., Weisenburger D. D. Nerve growth factor receptor expression on dendritic reticulum cells in follicular lymphoid proliferations. Hum Pathol. 1991 May;22(5):481–485. doi: 10.1016/0046-8177(91)90135-c. [DOI] [PubMed] [Google Scholar]
  48. Thompson S. J., Schatteman G. C., Gown A. M., Bothwell M. A monoclonal antibody against nerve growth factor receptor. Immunohistochemical analysis of normal and neoplastic human tissue. Am J Clin Pathol. 1989 Oct;92(4):415–423. doi: 10.1093/ajcp/92.4.415. [DOI] [PubMed] [Google Scholar]
  49. 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]
  50. Volpes R., Van Den Oord J. J., Desmet V. J. Vascular adhesion molecules in acute and chronic liver inflammation. Hepatology. 1992 Feb;15(2):269–275. doi: 10.1002/hep.1840150216. [DOI] [PubMed] [Google Scholar]
  51. Warnke R. A., Pulford K. A., Pallesen G., Ralfkiaer E., Brown D. C., Gatter K. C., Mason D. Y. Diagnosis of myelomonocytic and macrophage neoplasms in routinely processed tissue biopsies with monoclonal antibody KP1. Am J Pathol. 1989 Dec;135(6):1089–1095. [PMC free article] [PubMed] [Google Scholar]
  52. van Dinther-Janssen A. C., Horst E., Koopman G., Newmann W., Scheper R. J., Meijer C. J., Pals S. T. The VLA-4/VCAM-1 pathway is involved in lymphocyte adhesion to endothelium in rheumatoid synovium. J Immunol. 1991 Dec 15;147(12):4207–4210. [PubMed] [Google Scholar]
  53. van Seventer G. A., Newman W., Shimizu Y., Nutman T. B., Tanaka Y., Horgan K. J., Gopal T. V., Ennis E., O'Sullivan D., Grey H. Analysis of T cell stimulation by superantigen plus major histocompatibility complex class II molecules or by CD3 monoclonal antibody: costimulation by purified adhesion ligands VCAM-1, ICAM-1, but not ELAM-1. J Exp Med. 1991 Oct 1;174(4):901–913. doi: 10.1084/jem.174.4.901. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES