Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1994 Jul;62(7):2695–2701. doi: 10.1128/iai.62.7.2695-2701.1994

Soluble intercellular adhesion molecules in human schistosomiasis: correlations with disease severity and decreased responsiveness to egg antigens.

W E Secor 1, M G dos Reis 1, E A Ramos 1, E P Matos 1, E A Reis 1, T M do Carmo 1, D A Harn Jr 1
PMCID: PMC302870  PMID: 7516309

Abstract

Granuloma formation, the principal pathologic consequence of infection with Schistosoma mansoni, is a complex process involving intricate cell-cell interactions in which intercellular adhesion molecules are likely to participate. To examine this possibility, sera of schistosomiasis patients in various clinical groups were assayed for the presence of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble E-selectin (sE-selectin). Comparisons were made between groups with different infection intensities (as predicted by fecal egg count) as well as between groups with severe (hepatosplenic) or milder (intestinal) pathology. All groups had elevated levels of sICAM-1 compared with controls. Also, patients in the high egg-excreting and hepatosplenic groups had significantly higher levels of serum sICAM-1 than patients in the low-egg-excreting and intestinal groups, respectively. The levels of sE-selectin were significantly elevated in the sera of all patients except those in the hepatosplenic group compared with controls. Patients in the intestinal group had significantly higher levels of sE-selectin in their sera than did hepatosplenic group patients, but serum sE-selectin levels of high- and low-egg-excreting patients were comparable. A striking finding of this study was the inverse correlation observed between sICAM-1 levels and peripheral blood mononuclear cell responses to schistosome soluble egg antigens (SEA) but not with responses to other schistosome antigens, purified protein derivative, or mitogen. Because ICAM-1 can perform a costimulatory function in antigen-presenting cell-T cell interactions, it is possible that shedding of ICAM-1 in the granuloma microenvironment interrupts proper costimulation, leading to unresponsive SEA-specific T cells. In this way, sICAM-1 could be one factor contributing to the observed modulation of cellular responses to SEA in chronic human schistosomiasis.

Full text

PDF
2695

Selected References

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

  1. Amiri P., Locksley R. M., Parslow T. G., Sadick M., Rector E., Ritter D., McKerrow J. H. Tumour necrosis factor alpha restores granulomas and induces parasite egg-laying in schistosome-infected SCID mice. Nature. 1992 Apr 16;356(6370):604–607. doi: 10.1038/356604a0. [DOI] [PubMed] [Google Scholar]
  2. Becker J. C., Dummer R., Hartmann A. A., Burg G., Schmidt R. E. Shedding of ICAM-1 from human melanoma cell lines induced by IFN-gamma and tumor necrosis factor-alpha. Functional consequences on cell-mediated cytotoxicity. J Immunol. 1991 Dec 15;147(12):4398–4401. [PubMed] [Google Scholar]
  3. Becker J. C., Termeer C., Schmidt R. E., Bröcker E. B. Soluble intercellular adhesion molecule-1 inhibits MHC-restricted specific T cell/tumor interaction. J Immunol. 1993 Dec 15;151(12):7224–7232. [PubMed] [Google Scholar]
  4. Bensted-Smith R., Anderson R. M., Butterworth A. E., Dalton P. R., Kariuki H. C., Koech D., Mugambi M., Ouma J. H., arap Siongok T. K., Sturrock R. F. Evidence for predisposition of individual patients to reinfection with Schistosoma mansoni after treatment. Trans R Soc Trop Med Hyg. 1987;81(4):651–654. doi: 10.1016/0035-9203(87)90442-1. [DOI] [PubMed] [Google Scholar]
  5. Bevilacqua M. P. Endothelial-leukocyte adhesion molecules. Annu Rev Immunol. 1993;11:767–804. doi: 10.1146/annurev.iy.11.040193.004003. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Boussiotis V. A., Freeman G. J., Gray G., Gribben J., Nadler L. M. B7 but not intercellular adhesion molecule-1 costimulation prevents the induction of human alloantigen-specific tolerance. J Exp Med. 1993 Nov 1;178(5):1753–1763. doi: 10.1084/jem.178.5.1753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Boyd A. W., Wawryk S. O., Burns G. F., Fecondo J. V. Intercellular adhesion molecule 1 (ICAM-1) has a central role in cell-cell contact-mediated immune mechanisms. Proc Natl Acad Sci U S A. 1988 May;85(9):3095–3099. doi: 10.1073/pnas.85.9.3095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Butcher E. C. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell. 1991 Dec 20;67(6):1033–1036. doi: 10.1016/0092-8674(91)90279-8. [DOI] [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. Chensue S. W., Otterness I. G., Higashi G. I., Forsch C. S., Kunkel S. L. Monokine production by hypersensitivity (Schistosoma mansoni egg) and foreign body (Sephadex bead)-type granuloma macrophages. Evidence for sequential production of IL-1 and tumor necrosis factor. J Immunol. 1989 Feb 15;142(4):1281–1286. [PubMed] [Google Scholar]
  13. Chensue S. W., Terebuh P. D., Warmington K. S., Hershey S. D., Evanoff H. L., Kunkel S. L., Higashi G. I. Role of IL-4 and IFN-gamma in Schistosoma mansoni egg-induced hypersensitivity granuloma formation. Orchestration, relative contribution, and relationship to macrophage function. J Immunol. 1992 Feb 1;148(3):900–906. [PubMed] [Google Scholar]
  14. Colley D. G., Garcia A. A., Lambertucci J. R., Parra J. C., Katz N., Rocha R. S., Gazzinelli G. Immune responses during human schistosomiasis. XII. Differential responsiveness in patients with hepatosplenic disease. Am J Trop Med Hyg. 1986 Jul;35(4):793–802. [PubMed] [Google Scholar]
  15. Dougherty G. J., Murdoch S., Hogg N. The function of human intercellular adhesion molecule-1 (ICAM-1) in the generation of an immune response. Eur J Immunol. 1988 Jan;18(1):35–39. doi: 10.1002/eji.1830180107. [DOI] [PubMed] [Google Scholar]
  16. Dustin M. L., Rothlein R., Bhan A. K., Dinarello C. A., Springer T. A. Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol. 1986 Jul 1;137(1):245–254. [PubMed] [Google Scholar]
  17. Fecondo J. V., Kent S. B., Boyd A. W. Inhibition of intercellular adhesion molecule 1-dependent biological activities by a synthetic peptide analog. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2879–2882. doi: 10.1073/pnas.88.7.2879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fine D. P., Buchanan R. D., Colley D. G. Schistosoma mansoni infection in mice depleted of thymus-dependent lymphocytes. I. Eosinophilia and immunologic responses to a schistosomal egg preparation. Am J Pathol. 1973 May;71(2):193–206. [PMC free article] [PubMed] [Google Scholar]
  19. Fischer H., Gjörloff A., Hedlund G., Hedman H., Lundgren E., Kalland T., Sjögren H. O., Dohlsten M. Stimulation of human naive and memory T helper cells with bacterial superantigen. Naive CD4+45RA+ T cells require a costimulatory signal mediated through the LFA-1/ICAM-1 pathway. J Immunol. 1992 Apr 1;148(7):1993–1998. [PubMed] [Google Scholar]
  20. Furie M. B., Tancinco M. C., Smith C. W. Monoclonal antibodies to leukocyte integrins CD11a/CD18 and CD11b/CD18 or intercellular adhesion molecule-1 inhibit chemoattractant-stimulated neutrophil transendothelial migration in vitro. Blood. 1991 Oct 15;78(8):2089–2097. [PubMed] [Google Scholar]
  21. 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]
  22. Graber N., Gopal T. V., Wilson D., Beall L. D., Polte T., Newman W. T cells bind to cytokine-activated endothelial cells via a novel, inducible sialoglycoprotein and endothelial leukocyte adhesion molecule-1. J Immunol. 1990 Aug 1;145(3):819–830. [PubMed] [Google Scholar]
  23. Grober J. S., Bowen B. L., Ebling H., Athey B., Thompson C. B., Fox D. A., Stoolman L. M. Monocyte-endothelial adhesion in chronic rheumatoid arthritis. In situ detection of selectin and integrin-dependent interactions. J Clin Invest. 1993 Jun;91(6):2609–2619. doi: 10.1172/JCI116500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Henderson G. S., Lu X., McCurley T. L., Colley D. G. In vivo molecular analysis of lymphokines involved in the murine immune response during Schistosoma mansoni infection. II. Quantification of IL-4 mRNA, IFN-gamma mRNA, and IL-2 mRNA levels in the granulomatous livers, mesenteric lymph nodes, and spleens during the course of modulation. J Immunol. 1992 Apr 1;148(7):2261–2269. [PubMed] [Google Scholar]
  25. Joseph A. L., Boros D. L. Tumor necrosis factor plays a role in Schistosoma mansoni egg-induced granulomatous inflammation. J Immunol. 1993 Nov 15;151(10):5461–5471. [PubMed] [Google Scholar]
  26. Kuhlman P., Moy V. T., Lollo B. A., Brian A. A. The accessory function of murine intercellular adhesion molecule-1 in T lymphocyte activation. Contributions of adhesion and co-activation. J Immunol. 1991 Mar 15;146(6):1773–1782. [PubMed] [Google Scholar]
  27. Kyan-Aung U., Haskard D. O., Poston R. N., Thornhill M. H., Lee T. H. Endothelial leukocyte adhesion molecule-1 and intercellular adhesion molecule-1 mediate the adhesion of eosinophils to endothelial cells in vitro and are expressed by endothelium in allergic cutaneous inflammation in vivo. J Immunol. 1991 Jan 15;146(2):521–528. [PubMed] [Google Scholar]
  28. Lo S. K., Lee S., Ramos R. A., Lobb R., Rosa M., Chi-Rosso G., Wright S. D. Endothelial-leukocyte adhesion molecule 1 stimulates the adhesive activity of leukocyte integrin CR3 (CD11b/CD18, Mac-1, alpha m beta 2) on human neutrophils. J Exp Med. 1991 Jun 1;173(6):1493–1500. doi: 10.1084/jem.173.6.1493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Lobb R. R., Chi-Rosso G., Leone D. R., Rosa M. D., Bixler S., Newman B. M., Luhowskyj S., Benjamin C. D., Dougas I. G., Goelz S. E. Expression and functional characterization of a soluble form of endothelial-leukocyte adhesion molecule 1. J Immunol. 1991 Jul 1;147(1):124–129. [PubMed] [Google Scholar]
  30. Lukacs N. W., Boros D. L. Lymphokine regulation of granuloma formation in murine schistosomiasis mansoni. Clin Immunol Immunopathol. 1993 Jul;68(1):57–63. doi: 10.1006/clin.1993.1095. [DOI] [PubMed] [Google Scholar]
  31. Marlin S. D., Staunton D. E., Springer T. A., Stratowa C., Sommergruber W., Merluzzi V. J. A soluble form of intercellular adhesion molecule-1 inhibits rhinovirus infection. Nature. 1990 Mar 1;344(6261):70–72. doi: 10.1038/344070a0. [DOI] [PubMed] [Google Scholar]
  32. Mathew R. C., Boros D. L. Anti-L3T4 antibody treatment suppresses hepatic granuloma formation and abrogates antigen-induced interleukin-2 production in Schistosoma mansoni infection. Infect Immun. 1986 Dec;54(3):820–826. doi: 10.1128/iai.54.3.820-826.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Moy V. T., Brian A. A. Signaling by lymphocyte function-associated antigen 1 (LFA-1) in B cells: enhanced antigen presentation after stimulation through LFA-1. J Exp Med. 1992 Jan 1;175(1):1–7. doi: 10.1084/jem.175.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Mueller D. L., Jenkins M. K., Schwartz R. H. Clonal expansion versus functional clonal inactivation: a costimulatory signalling pathway determines the outcome of T cell antigen receptor occupancy. Annu Rev Immunol. 1989;7:445–480. doi: 10.1146/annurev.iy.07.040189.002305. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. Phillips S. M., DiConza J. J., Gold J. A., Reid W. A. Schistosomiasis in the congenitally athymic (nude) mouse. I. Thymic dependency of eosinophilia, granuloma formation, and host morbidity. J Immunol. 1977 Feb;118(2):594–599. [PubMed] [Google Scholar]
  37. Picker L. J., Kishimoto T. K., Smith C. W., Warnock R. A., Butcher E. C. ELAM-1 is an adhesion molecule for skin-homing T cells. Nature. 1991 Feb 28;349(6312):796–799. doi: 10.1038/349796a0. [DOI] [PubMed] [Google Scholar]
  38. Pigott R., Dillon L. P., Hemingway I. H., Gearing A. J. Soluble forms of E-selectin, ICAM-1 and VCAM-1 are present in the supernatants of cytokine activated cultured endothelial cells. Biochem Biophys Res Commun. 1992 Sep 16;187(2):584–589. doi: 10.1016/0006-291x(92)91234-h. [DOI] [PubMed] [Google Scholar]
  39. Pizzolo G., Vinante F., Nadali G., Ricetti M. M., Morosato L., Marrocchella R., Vincenzi C., Semenzato G., Chilosi M. ICAM-1 tissue overexpression associated with increased serum levels of its soluble form in Hodgkin's disease. Br J Haematol. 1993 May;84(1):161–162. doi: 10.1111/j.1365-2141.1993.tb03040.x. [DOI] [PubMed] [Google Scholar]
  40. Rothlein R., Mainolfi E. A., Czajkowski M., Marlin S. D. A form of circulating ICAM-1 in human serum. J Immunol. 1991 Dec 1;147(11):3788–3793. [PubMed] [Google Scholar]
  41. Scheynius A., Camp R. L., Puré E. Reduced contact sensitivity reactions in mice treated with monoclonal antibodies to leukocyte function-associated molecule-1 and intercellular adhesion molecule-1. J Immunol. 1993 Jan 15;150(2):655–663. [PubMed] [Google Scholar]
  42. Schwartz R. H. A cell culture model for T lymphocyte clonal anergy. Science. 1990 Jun 15;248(4961):1349–1356. doi: 10.1126/science.2113314. [DOI] [PubMed] [Google Scholar]
  43. Shimizu Y., Newman W., Gopal T. V., Horgan K. J., Graber N., Beall L. D., van Seventer G. A., Shaw S. Four molecular pathways of T cell adhesion to endothelial cells: roles of LFA-1, VCAM-1, and ELAM-1 and changes in pathway hierarchy under different activation conditions. J Cell Biol. 1991 Jun;113(5):1203–1212. doi: 10.1083/jcb.113.5.1203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Shimizu Y., Shaw S., Graber N., Gopal T. V., Horgan K. J., Van Seventer G. A., Newman W. Activation-independent binding of human memory T cells to adhesion molecule ELAM-1. Nature. 1991 Feb 28;349(6312):799–802. doi: 10.1038/349799a0. [DOI] [PubMed] [Google Scholar]
  45. Springer T. A. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. doi: 10.1038/346425a0. [DOI] [PubMed] [Google Scholar]
  46. Springer T. A., Dustin M. L., Kishimoto T. K., Marlin S. D. The lymphocyte function-associated LFA-1, CD2, and LFA-3 molecules: cell adhesion receptors of the immune system. Annu Rev Immunol. 1987;5:223–252. doi: 10.1146/annurev.iy.05.040187.001255. [DOI] [PubMed] [Google Scholar]
  47. St Louis J. D., Lederer J. A., Lichtman A. H. Costimulator deficient antigen presentation by an endothelial cell line induces a nonproliferative T cell activation response without anergy. J Exp Med. 1993 Nov 1;178(5):1597–1605. doi: 10.1084/jem.178.5.1597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. 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]
  49. Stoolman L. M. Adhesion molecules controlling lymphocyte migration. Cell. 1989 Mar 24;56(6):907–910. doi: 10.1016/0092-8674(89)90620-x. [DOI] [PubMed] [Google Scholar]
  50. Tracey K. J., Cerami A. Tumor necrosis factor and regulation of metabolism in infection: role of systemic versus tissue levels. Proc Soc Exp Biol Med. 1992 Jun;200(2):233–239. doi: 10.3181/00379727-200-43426. [DOI] [PubMed] [Google Scholar]
  51. Van Seventer G. A., Shimizu Y., Horgan K. J., Shaw S. The LFA-1 ligand ICAM-1 provides an important costimulatory signal for T cell receptor-mediated activation of resting T cells. J Immunol. 1990 Jun 15;144(12):4579–4586. [PubMed] [Google Scholar]
  52. Weller P. F., Rand T. H., Goelz S. E., Chi-Rosso G., Lobb R. R. Human eosinophil adherence to vascular endothelium mediated by binding to vascular cell adhesion molecule 1 and endothelial leukocyte adhesion molecule 1. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7430–7433. doi: 10.1073/pnas.88.16.7430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Zwingenberger K., Irschick E., Vergetti Siqueira J. G., Correia Dacal A. R., Feldmeier H. Tumour necrosis factor in hepatosplenic schistosomiasis. Scand J Immunol. 1990 Feb;31(2):205–211. doi: 10.1111/j.1365-3083.1990.tb02761.x. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES