Skip to main content
SpringerLink
Log in

Pharmacological Targeting of ICAM-1 Signaling in Brain Endothelial Cells: Potential for Treating Neuroinflammation

  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Summary

1. The vasculature of the blood–brain barrier allows only comparatively few leukocytes to enter and survey the healthy central nervous system (CNS). However, during pathological CNS inflammation, the number of leukocytes adhering to and penetrating the CNS vasculature increases strongly.

2. Endothelial adhesion molecules do not only mediate firm adhesion of leukocyte to vascular beds but also trigger signaling cascades within the endothelial cell, which play a crucial role in modulating subsequent leukocyte diapedesis.

3. Signaling through endothelial intercellular adhesion molecule-1 (ICAM-1, CD54) has been shown to induce changes of the endothelial cytoskeleton, transcription, and interendothelial junctions, all of which may be important in modulating endothelial disposition to infiltrating leukocytes. Furthermore, a number of recent reports document that drugs interfering with endothelial ICAM-1 signaling, efficiently reduce leukocyte migration both in vitro and in animal models of CNS inflammation.

4. These approaches are novel in as much as they target vascular beds rather than the penetrating leukocytes. Since endothelial ICAM-1 signaling appears to differ between different vascular beds we propose that such compounds could potentially be used as exquisite drugs in the treatment of neuroinflammatory diseases.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adamson, P., Etienne, S., Couraud, P. O., Calder, V., and Greenwood, J. (1999). Lymphocyte migration through brain endothelial cell monolayers involves signaling through endothelial ICAM-1 via a rho-dependent pathway. J. Immunol. 162:2964–2973.

    PubMed  CAS  Google Scholar 

  • Adamson, P., Marshall, C. J., Hall, A., and Tilbrook, P. A. (1992). Post-translational modifications of p21rho proteins. J. Biol. Chem. 267:20033–20038.

    PubMed  CAS  Google Scholar 

  • Aktas, O., Waiczies, S., Smorodchenko, A., Dorr, J., Seeger, B., Prozorovski, T., Sallach, S., Endres, M., Brocke, S., Nitsch, R., and Zipp, F. (2003). Treatment of relapsing paralysis in experimental encephalomyelitis by targeting Th1 cells through atorvastatin. J. Exp. Med. 197:725–733.

    Article  PubMed  CAS  Google Scholar 

  • Amos, C., Romero, I. A., Schultze, C., Rousell, J., Pearson, J. D., Greenwood, J., and Adamson, P. (2001). Cross-linking of brain endothelial intercellular adhesion molecule (ICAM)-1 induces association of ICAM-1 with detergent-insoluble cytoskeletal fraction. Arterioscler. Thromb. Vasc. Biol. 21:810–816.

    PubMed  CAS  Google Scholar 

  • Archelos, J. J., Jung, S., Maurer, M., Schmied, M., Lassmann, H., Tamatani, T., Miyasaka, M., Toyka, K. V., and Hartung, H. P. (1993). Inhibition of experimental autoimmune encephalomyelitis by an antibody to the intercellular adhesion molecule ICAM-1. Ann. Neurol. 34:145–154.

    Article  PubMed  CAS  Google Scholar 

  • Barreiro, O., Yanez-Mo, M., Serrador, J. M., Montoya, M. C., Vicente-Manzanares, M., Tejedor, R., Furthmayr, H., and Sanchez-Madrid, F. (2002). Dynamic interaction of VCAM-1 and ICAM-1 with moesin and ezrin in a novel endothelial docking structure for adherent leukocytes. J. Cell Biol. 157:1233–1245.

    Article  PubMed  CAS  Google Scholar 

  • Brandt, D., Gimona, M., Hillmann, M., Haller, H., and Mischak, H. (2002). Protein kinase C induces actin reorganization via a Src- and Rho-dependent pathway. J. Biol. Chem. 277:20903–20910.

    Article  PubMed  CAS  Google Scholar 

  • Bretscher, A., Edwards, K., and Fehon, R. G. (2002). ERM proteins and merlin: Integrators at the cell cortex. Nat. Rev. Mol. Cell Biol. 3:586–599.

    Article  PubMed  CAS  Google Scholar 

  • Calder, V., and Greenwood, J. (1995). Role of the vascular endothelium in immunologically mediated neurological disease. In Savage, C., and Pearson, J. D. (eds.), Immunological Aspects of the Vascular Endothelium, Cambridge University Press, Cambridge, pp. 96–123.

    Google Scholar 

  • Cannella, B., Cross, A. H., and Raine, C. S. (1993). Anti-adhesion molecule therapy in experimental autoimmune encephalomyelitis. J. Neuroimmunol. 46:43–55.

    Article  PubMed  CAS  Google Scholar 

  • Carpen, O., Pallai, P., Staunton, D. E., and Springer, T. A. (1992). Association of intercellular adhesion molecule-1 (ICAM-1) with actin-containing cytoskeleton and alpha-actinin. J. Cell Biol. 118:1223–1234.

    Article  PubMed  CAS  Google Scholar 

  • Carman, C. V., Jun, C. D., Salas, A., and Springer, T. A. (2003). Endothelial cells proactively from microvilli-like membrane projections upon intercellular adhesion molecule 1 engagement of leukocyte LFA-1. J. Immunol. 171:6135–6144.

    PubMed  CAS  Google Scholar 

  • Chang, L., and Karin, M. (2001). Mammalian MAP kinase signalling cascades. Nature 410:37–40.

    Article  PubMed  CAS  Google Scholar 

  • Clayton, A., Evans, R. A., Pettit, E., Hallett, M., Williams, J. D., and Steadman, R. (1998). Cellular activation through the ligation of intercellular adhesion molecule-1. J. Cell Sci. 111:443–453.

    PubMed  CAS  Google Scholar 

  • Constantin, G., Laudanna, C., Brocke, S., and Butcher, E. C. (1999). Inhibition of experimental autoimmune encephalomyelitis by a tyrosine kinase inhibitor. J. Immunol. 162:1144–1149.

    PubMed  CAS  Google Scholar 

  • Cronstein, B. N., Kimmel, S. C., Levin, R. I., Martiniuk, F., and Weissmann, G. (1992). A mechanism for the antiinflammatory effects of corticosteroids: The glucocorticoid receptor regulates leukocyte adhesion to endothelial cells and expression of endothelial-leukocyte adhesion molecule 1 and intercellular adhesion molecule 1. Proc. Natl. Acad. Sci. USA 89:9991–9995.

    Article  PubMed  CAS  Google Scholar 

  • Defazio, G., Livrea, P., Giorelli, M., Martino, D., Roselli, F., Ricchiuti, F., and Trojano, M. (2000). Interferon beta-1a downregulates TNFalpha-induced intercellular adhesion molecule 1 expression on brain microvascular endothelial cells through a tyrosine kinase-dependent pathway. Brain Res. 881:227–230.

    Article  PubMed  CAS  Google Scholar 

  • Del Maschio, A., De Luigi, A., Martin-Padura, I., Brockhaus, M., Bartfai, T., Fruscella, P., Adorini, L., Martino, G., Furlan, R., De Simoni, M. G., and Dejana, E. (1999). Leukocyte recruitment in the cerebrospinal fluid of mice with experimental meningitis is inhibited by an antibody to junctional adhesion molecule (JAM). J. Exp. Med. 190:1351–1356.

    Article  PubMed  CAS  Google Scholar 

  • Dietrich, J. B. (2002). The adhesion molecule ICAM-1 and its regulation in relation with the blood–brain barrier. J. Neuroimmunol. 128:58–68.

    Article  PubMed  CAS  Google Scholar 

  • Durieu-Trautmann, O., Chaverot, N., Cazaubon, S., Strosberg, A. D., and Couraud, P. O. (1994). Intercellular adhesion molecule 1 activation induces tyrosine phosphorylation of the cytoskeleton-associated protein cortactin in brain microvessel endothelial cells. J. Biol. Chem. 269:12536–12540.

    PubMed  CAS  Google Scholar 

  • Etienne, S., Adamson, P., Greenwood, J., Strosberg, A. D., Cazaubon, S., and Couraud, P. O. (1998). ICAM-1 signaling pathways associated with Rho activation in microvascular brain endothelial cells. J. Immunol. 161:5755–5761.

    PubMed  CAS  Google Scholar 

  • Etienne-Manneville, S., Chaverot, N., Strosberg, A. D., and Couraud, P. O. (1999). ICAM-1-coupled signaling pathways in astrocytes converge to cyclic AMP response element-binding protein phosphorylation and TNF-alpha secretion. J. Immunol. 163:668–674.

    PubMed  CAS  Google Scholar 

  • Etienne-Manneville, S., and Hall, A. (2002). Rho GTPases in cell biology. Nature 420:629–635.

    Article  PubMed  CAS  Google Scholar 

  • Etienne-Manneville, S., Manneville, J. B., Adamson, P., Wilbourn, B., Greenwood, J., and Couraud, P. O. (2000). ICAM-1-coupled cytoskeletal rearrangements and transendothelial lymphocyte migration involve intracellular calcium signaling in brain endothelial cell lines. J. Immunol. 165:3375–3383.

    PubMed  CAS  Google Scholar 

  • Fabry, Z., Waldschmidt, M. M., Hendrickson, D., Keiner, J., Love-Homan, L., Takei, F., and Hart, M. N. (1992). Adhesion molecules on murine brain microvascular endothelial cells: Expression and regulation of ICAM-1 and Lgp 55. J. Neuroimmunol. 36:1–11.

    Article  PubMed  CAS  Google Scholar 

  • Federici, C., Camoin, L., Hattab, M., Strosberg, A. D., and Couraud, P. O. (1996). Association of the cytoplasmic domain of intercellular-adhesion molecule-1 with glyceraldehyde-3-phosphate dehydrogenase and beta-tubulin. Eur. J. Biochem. 238:173–180.

    Article  PubMed  CAS  Google Scholar 

  • Floris, S., Ruuls, S. R., Wierinckx, A., van der Pol, S. M., Dopp, E., van der Meide, P. H., Dijkstra, C. D., and De Vries, H. E. (2002). Interferon-beta directly influences monocyte infiltration into the central nervous system. J. Neuroimmunol. 127:69–79.

    Article  PubMed  CAS  Google Scholar 

  • Gardiner, E. E., and D’Souza, S. E. (1997). A mitogenic action for fibrinogen mediated through intercellular adhesion molecule-1. J. Biol. Chem. 272:15474–15480.

    Article  PubMed  CAS  Google Scholar 

  • Gautreau, A., Louvard, D., and Arpin, M. (2002). ERM proteins and NF2 tumor suppressor: The Yin and Yang of cortical actin organization and cell growth signaling. Curr. Opin. Cell Biol. 14:104–109.

    Article  PubMed  CAS  Google Scholar 

  • Greenwood, J., Etienne-Manneville, S., Adamson, P., and Couraud, P. O. (2002). Lymphocyte migration into the central nervous system: Implication of ICAM-1 signalling at the blood–brain barrier. Vascul. Pharmacol. 38:315–322.

    Article  PubMed  CAS  Google Scholar 

  • Greenwood, J., Amos, C. L., Walters, C. E., Couraud, P. O., Lyck, R., Engelhardt, B., and Adamson, P. (2003a). Intracellular domain of brain endothelial ICAM-1 is essential for T lymphocyte-mediated signaling and migration. J. Immunol. 171:2099–2108.

    CAS  Google Scholar 

  • Greenwood, J., Walters, C. E., Pryce, G., Kanuga, N., Beraud, E., Baker, D., and Adamson, P. (2003b). Lovastatin inhibits brain endothelial cell Rho-mediated lymphocyte migration and attenuates experimental autoimmune encephalomyelitis. FASEB J. 17:905–907.

    CAS  Google Scholar 

  • Greenwood, J., Wang, Y., and Calder, V. L. (1995). Lymphocyte adhesion and transendothelial migration in the central nervous system: The role of LFA-1, ICAM-1, VLA-4 and VCAM-1. Immunology 86:408–415.

    PubMed  CAS  Google Scholar 

  • Hanks, S. K., Ryzhova, L., Shin, N. Y., and Brabek, J. (2003). Focal adhesion kinase signaling activities and their implications in the control of cell survival and motility. Front Biosci. 8:D982–D996.

    Article  PubMed  CAS  Google Scholar 

  • Heiska, L., Alfthan, K., Gronholm, M., Vilja, P., Vaheri, A., and Carpen, O. (1998). Association of ezrin with intercellular adhesion molecule-1 and -2 (ICAM-1 and ICAM-2). Regulation by phosphatidylinositol 4, 5-bisphosphate. J. Biol. Chem. 273:21893–21900.

    Article  PubMed  CAS  Google Scholar 

  • Hickey, W. F. (1999). Leukocyte traffic in the central nervous system: The participants and their roles. Semin. Immunol. 11:125–137.

    Article  PubMed  CAS  Google Scholar 

  • Hickey, W. F. (2001). Basic principles of immunological surveillance of the normal central nervous system. Glia 36:118–124.

    Article  PubMed  CAS  Google Scholar 

  • Hirase, T., Staddon, J. M., Saitou, M., Ando-Akatsuka, Y., Itoh, M., Furuse, M., Fujimoto, K., Tsukita, S., and Rubin, L. L. (1997). Occludin as a possible determinant of tight junction permeability in endothelial cells. J. Cell Sci. 110:1603–1613.

    PubMed  CAS  Google Scholar 

  • Holland, J., and Owens, T. (1997). Signaling through intercellular adhesion molecule 1 (ICAM-1) in a B cell lymphoma line. The activation of Lyn tyrosine kinase and the mitogen-activated protein kinase pathway. J. Biol. Chem. 272:9108–9112.

    Article  PubMed  CAS  Google Scholar 

  • Hordijk, P. (2003). Endothelial signaling in leukocyte transmigration. Cell Biochem. Biophys. 38:305–322.

    Article  PubMed  CAS  Google Scholar 

  • Huang, A. J., Manning, J. E., Bandak, T. M., Ratau, M. C., Hanser, K. R., and Silverstein, S. C. (1993). Endothelial cell cytosolic free calcium regulates neutrophil migration across monolayers of endothelial cells. J. Cell Biol. 120:13710–1380.

    Article  Google Scholar 

  • Hubbard, A. K., and Rothlein, R. (2000). Intercellular adhesion molecule-1 (ICAM-1) expression and cell signaling cascades. Free Radic. Biol. Med. 28:1379–1386.

    Article  PubMed  CAS  Google Scholar 

  • Huber, D., Balda, M. S., and Matter, K. (2000). Occludin modulates transepithelial migration of neutrophils. J. Biol. Chem. 275:5773–5778.

    Article  PubMed  CAS  Google Scholar 

  • Kobashigawa, J. A., Katznelson, S., Laks, H., Johnson, J. A., Yeatman, L., Wang, X. M., Chia, D., Terasaki, P. I., Sabad, A., Cogert, G. A., Trosian, K., Hamilton, M. A., Moriguchi, J. D., Kawata, N., Hage, A., Drinkwater, D. C., and Stevenson, L. W. (1995). Effect of pravastatin on outcomes after cardiac transplantation. N. Engl. J. Med. 333:621–627.

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi, Y., Kawai, K., Honda, H., Tomida, S., Niimi, N., Tamatani, T., Miyasaka, M., and Yoshikai, Y. (1995). Antibodies against leukocyte function-associated antigen-1 and against intercellular adhesion molecule-1 together suppress the progression of experimental allergic encephalomyelitis. Cell Immunol. 164:295–305.

    Article  PubMed  CAS  Google Scholar 

  • Laschinger, M., Vajkoczy, P., and Engelhardt, B. (2002). Encephalitogenic T cells use LFA-1 for transendothelial migration but not during capture and initial adhesion strengthening in healthy spinal cord microvessels in vivo. Eur. J. Immunol. 32:3598–3606.

    Article  PubMed  CAS  Google Scholar 

  • Lawson, C., Ainsworth, M., Yacoub, M., and Rose, M. (1999). Ligation of ICAM-1 on endothelial cells leads to expression of VCAM-1 via a nuclear factor-kappaB-independent mechanism. J. Immunol. 162:2990–2996.

    PubMed  CAS  Google Scholar 

  • Linke, A. T., Antonopoulos, M., Davies, D. H., and Male, D. K. (2000). Strain specific variation in cytokine regulated ICAM-1 expression by rat brain-endothelial cells. J. Neuroimmunol. 104:10–14.

    Article  PubMed  CAS  Google Scholar 

  • Lorenzon, P., Vecile, E., Nardon, E., Ferrero, E., Harlan, J. M., Tedesco, F., and Dobrina, A. (1998). Endothelial cell E- and P-selectin and vascular cell adhesion molecule-1 function as signaling receptors. J. Cell Biol. 142:1381–1391.

    Article  PubMed  CAS  Google Scholar 

  • Lou, J., Chofflon, M., Juillard, C., Donati, Y., Mili, N., Siegrist, C. A., and Grau, G. E. (1997). Brain microvascular endothelial cells and leukocytes derived from patients with multiple sclerosis exhibit increased adhesion capacity. Neuroreport 8:629–633.

    Article  PubMed  CAS  Google Scholar 

  • Lyck, R., Reiss, Y., Gerwin, N., Greenwood, J., Adamson, P., and Engelhardt, B. (2003). T-cell interaction with ICAM-1/ICAM-2 double-deficient brain endothelium in vitro: The cytoplasmic tail of endothelial ICAM-1 is necessary for transendothelial migration of T-cells. Blood 102:3675–3683.

    Article  PubMed  CAS  Google Scholar 

  • Male, D., Rahman, J., Pryce, G., Tamatani, T., and Miyasaka, M. (1994). Lymphocyte migration into the CNS modelled in vitro: Roles of LFA-1, ICAM-1 and VLA-4. Immunology 81:366–372.

    PubMed  CAS  Google Scholar 

  • Martin-Padura, I., Lostaglio, S., Schneemann, M., Williams, L., Romano, M., Fruscella, P., Panzeri, C., Stoppacciaro, A., Ruco, L., Villa, A., Simmons, D., and Dejana, E. (1998). Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration. J. Cell Biol. 142:117–127.

    Article  PubMed  CAS  Google Scholar 

  • Matter, K., and Balda, M. S. (2003). Signalling to and from tight junctions. Nat. Rev. Mol. Cell Biol. 4:225–236.

    Article  PubMed  CAS  Google Scholar 

  • Middleton, J., Patterson, A. M., Gardner, L., Schmutz, C., and Ashton, B. A. (2002). Leukocyte extravasation: Chemokine transport and presentation by the endothelium. Blood 100:3853–3860.

    Article  PubMed  CAS  Google Scholar 

  • Miller, D. H., Khan, O. A., Sheremata, W. A., Blumhardt, L. D., Rice, G. P., Libonati, M. A., Willmer-Hulme, A. J., Dalton, C. M., Miszkiel, K. A., and O’Connor, P. W. (2003). A controlled trial of natalizumab for relapsing multiple sclerosis. N. Engl. J. Med. 348:15–23.

    Article  PubMed  CAS  Google Scholar 

  • Montoya, M. C., Sancho, D., Vicente-Manzanares, M., and Sanchez-Madrid, F. (2002). Cell adhesion and polarity during immune interactions. Immunol. Rev. 186:68–82.

    Article  PubMed  CAS  Google Scholar 

  • Morrissey, S. P., Deichmann, R., Syha, J., Simonis, C., Zettl, U., Archelos, J. J., Jung, S., Stodal, H., Lassmann, H., Toyka, K. V., Haase, A., and Hartung, H. P. (1996). Partial inhibition of AT-EAE by an antibody to ICAM-1: Clinico-histological and MRI studies. J. Neuroimmunol. 69:85–93.

    Article  PubMed  CAS  Google Scholar 

  • Muller, W. A. (1995). The role of PECAM-1 (CD31) in leukocyte emigration: Studies in vitro and in vivo. J. Leukoc. Biol. 57:523–528.

    PubMed  CAS  Google Scholar 

  • Neel, B. G., and Tonks, N. K. (1997). Protein tyrosine phosphatases in signal transduction. Curr. Opin. Cell Biol. 9:193–204.

    Article  PubMed  CAS  Google Scholar 

  • O’Neill, J. K., Butter, C., Baker, D., Gschmeissner, S. E., Kraal, G., Butcher, E. C., and Turk, J. L. (1991). Expression of vascular addressins and ICAM-1 by endothelial cells in the spinal cord during chronic relapsing experimental allergic encephalomyelitis in the Biozzi AB/H mouse. Immunology 72:520–525.

    PubMed  CAS  Google Scholar 

  • Pahan, K., Sheikh, F. G., Namboodiri, A. M., and Singh, I. (1997). Lovastatin and phenylacetate inhibit the induction of nitric oxide synthase and cytokines in rat primary astrocytes, microglia, and macrophages. J. Clin. Invest 100:2671–2679.

    Article  PubMed  CAS  Google Scholar 

  • Perry, V. H., Anthony, D. C., Bolton, S. J., and Brown, H. C. (1997). The blood–brain barrier and the inflammatory response. Mol. Med. Today 3:335–341.

    Article  PubMed  CAS  Google Scholar 

  • Pfau, S., Leitenberg, D., Rinder, H., Smith, B. R., Pardi, R., and Bender, J. R. (1995). Lymphocyte adhesion-dependent calcium signaling in human endothelial cells. J. Cell Biol. 128:969–978.

    Article  PubMed  CAS  Google Scholar 

  • Pluskota, E., Chen, Y., and D’Souza, S. E. (2000). Src homology domain 2-containing tyrosine phosphatase 2 associates with intercellular adhesion molecule 1 to regulate cell survival. J. Biol. Chem. 275:30029–30036.

    Article  PubMed  CAS  Google Scholar 

  • Pluskota, E., and D’Souza, S. E. (2000). Fibrinogen interactions with ICAM-1 (CD54) regulate endothelial cell survival. Eur. J. Biochem. 267:4693–4704.

    Article  PubMed  CAS  Google Scholar 

  • Poudrier, J., and Owens, T. (1994). CD54/intercellular adhesion molecule 1 and major histocompatibility complex II signaling induces B cells to express interleukin 2 receptors and complements help provided through CD40 ligation. J. Exp. Med. 179:1417–1427.

    Article  PubMed  CAS  Google Scholar 

  • Prendergast, G. C. (2000). Farnesyltransferase inhibitors: Antineoplastic mechanism and clinical prospects. Curr. Opin. Cell Biol. 12:166–173.

    Article  PubMed  CAS  Google Scholar 

  • Pryce, G., Male, D., Campbell, I., and Greenwood, J. (1997). Factors controlling T-cell migration across rat cerebral endothelium in vitro. J. Neuroimmunol. 75:84–94.

    Article  PubMed  CAS  Google Scholar 

  • Reiss, Y., and Engelhardt, B. (1999). T cell interaction with ICAM-1-deficient endothelium in vitro: Transendothelial migration of different T cell populations is mediated by endothelial ICAM-1 and ICAM-2. Int. Immunol. 11:1527–1539.

    Article  PubMed  CAS  Google Scholar 

  • Ricard, I., Payet, M. D., and Dupuis, G. (1997). Clustering the adhesion molecules VLA-4 (CD49d/CD29) in Jurkat T cells or VCAM-1 (CD106) in endothelial (ECV 304) cells activates the phosphoinositide pathway and triggers Ca2+ mobilization. Eur. J. Immunol. 27:1530–1538.

    Article  PubMed  CAS  Google Scholar 

  • Ridley, A. J. (2001). Rho family proteins: Coordinating cell responses. Trends Cell Biol. 11:471–477.

    Article  PubMed  CAS  Google Scholar 

  • Rose, J. W., Welsh, C. T., Hill, K. E., Houtchens, M. K., Fujinami, R. S., and Townsend, J. J. (1999). Contrasting effects of anti-adhesion molecule therapy in experimental allergic encephalomyelitis and Theiler’s murine encephalomyelitis. J. Neuroimmunol. 97:110–118.

    Article  PubMed  CAS  Google Scholar 

  • Rothlein, R., Kishimoto, T. K., and Mainolfi, E. (1994). Cross-linking of ICAM-1 induces co-signaling of an oxidative burst from mononuclear leukocytes. J. Immunol. 152:2488–2495.

    PubMed  CAS  Google Scholar 

  • Rubin, L. L., and Staddon, J. M. (1999). The cell biology of the blood–brain barrier. Annu. Rev. Neurosci. 22:11–28.

    Article  PubMed  CAS  Google Scholar 

  • Saito, H., Minamiya, Y., Kitamura, M., Saito, S., Enomoto, K., Terada, K., and Ogawa, J. (1998). Endothelial myosin light chain kinase regulates neutrophil migration across human umbilical vein endothelial cell monolayer. J. Immunol. 161:1533–1540.

    PubMed  CAS  Google Scholar 

  • Sano, H., Nakagawa, N., Chiba, R., Kurasawa, K., Saito, Y., and Iwamoto, I. (1998). Cross-linking of intercellular adhesion molecule-1 induces interleukin-8 and RANTES production through the activation of MAP kinases in human vascular endothelial cells. Biochem. Biophys. Res. Commun. 250:694–698.

    Article  PubMed  CAS  Google Scholar 

  • Sans, E., Delachanal, E., and Duperray, A. (2001). Analysis of the roles of ICAM-1 in neutrophil transmigration using a reconstituted mammalian cell expression model: Implication of ICAM-1 cytoplasmic domain and Rho-dependent signaling pathway. J. Immunol. 166:544–551.

    PubMed  CAS  Google Scholar 

  • Sligh, J. E., Jr., Ballantyne, C. M., Rich, S. S., Hawkins, H. K., Smith, C. W., Bradley, A., and Beaudet, A. L. (1993). Inflammatory and immune responses are impaired in mice deficient in intercellular adhesion molecule 1. Proc. Natl. Acad. Sci. USA 90:8529–8533.

    Article  PubMed  CAS  Google Scholar 

  • Sobel, R. A., Mitchell, M. E., and Fondren, G. (1990). Intercellular adhesion molecule-1 (ICAM-1) in cellular immune reactions in the human central nervous system. Am. J. Pathol. 136:1309–1316.

    PubMed  CAS  Google Scholar 

  • Springer, T. A. (1990). Adhesion receptors of the immune system. Nature 346:425–434.

    Article  PubMed  CAS  Google Scholar 

  • Springer, T. A. (1994). Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm. Cell 76:301–314.

    Article  PubMed  CAS  Google Scholar 

  • Stanislaus, R., Gilg, A. G., Singh, A. K., and Singh, I. (2002). Immunomodulation of experimental autoimmune encephalomyelitis in the Lewis rats by Lovastatin. Neurosci. Lett. 333:167–170.

    Article  PubMed  CAS  Google Scholar 

  • Stanislaus, R., Pahan, K., Singh, A. K., and Singh, I. (1999). Amelioration of experimental allergic encephalomyelitis in Lewis rats by lovastatin. Neurosci. Lett. 269:71–74.

    Article  PubMed  CAS  Google Scholar 

  • Stanislaus, R., Singh, A. K., and Singh, I. (2001). Lovastatin treatment decreases mononuclear cell infiltration into the CNS of Lewis rats with experimental allergic encephalomyelitis. J. Neurosci. Res. 66:155–162.

    Article  PubMed  CAS  Google Scholar 

  • Steeber, D. A., Tang, M. L., Green, N. E., Zhang, X. Q., Sloane, J. E., and Tedder, T. F. (1999). Leukocyte entry into sites of inflammation requires overlapping interactions between the L-selectin and ICAM-1 pathways. J. Immunol. 163:2176–2186.

    PubMed  CAS  Google Scholar 

  • Strey, A., Janning, A., Barth, H., and Gerke, V. (2002). Endothelial Rho signaling is required for monocyte transendothelial migration. FEBS Lett. 517:261–266.

    Article  PubMed  CAS  Google Scholar 

  • Stuve, O., Youssef, S., Steinman, L., and Zamvil, S. S. (2003). Statins as potential therapeutic agents in neuroinflammatory disorders. Curr. Opin. Neurol. 16:393–401.

    Article  PubMed  Google Scholar 

  • Thompson, P. W., Randi, A. M., and Ridley, A. J. (2002). Intercellular adhesion molecule (ICAM)-1, but not ICAM-2, activates RhoA and stimulates c-fos and rhoA transcription in endothelial cells. J. Immunol. 169:1007–1013.

    PubMed  CAS  Google Scholar 

  • Tilghman, R. W., and Hoover, R. L. (2002a). E-selectin and ICAM-1 are incorporated into detergent-insoluble membrane domains following clustering in endothelial cells. FEBS Lett. 525:83–87.

    Article  CAS  Google Scholar 

  • Tilghman, R. W., and Hoover, R. L. (2002b). The Src-cortactin pathway is required for clustering of E-selectin and ICAM-1 in endothelial cells. FASEB J. 16:1257–1259.

    CAS  Google Scholar 

  • Tsakadze, N. L., Zhao, Z., and D’Souza, S. E. (2002). Interactions of intercellular adhesion molecule-1 with fibrinogen. Trends Cardiovasc. Med. 12:101–108.

    Article  PubMed  CAS  Google Scholar 

  • Vajkoczy, P., Laschinger, M., and Engelhardt, B. (2001). Alpha4-integrin-VCAM-1 binding mediates G protein-independent capture of encephalitogenic T cell blasts to CNS white matter microvessels. J. Clin. Invest 108:557–565.

    PubMed  CAS  Google Scholar 

  • Van der Goes, A., Wouters, D., Van Der Pol, S. M., Huizinga, R., Ronken, E., Adamson, P., Greenwood, J., Dijkstra, C. D., and De Vries, H. E. (2001). Reactive oxygen species enhance the migration of monocytes across the blood–brain barrier in vitro. FASEB J. 15:1852–1854.

    PubMed  CAS  Google Scholar 

  • Walters, C. E., Pryce, G., Hankey, D. J., Sebti, S. M., Hamilton, A. D., Baker, D., Greenwood, J., and Adamson, P. (2002). Inhibition of Rho GTPases with protein prenyltransferase inhibitors prevents leukocyte recruitment to the central nervous system and attenuates clinical signs of disease in an animal model of multiple sclerosis. J. Immunol. 168:4087–4094.

    PubMed  CAS  Google Scholar 

  • Wang, Q., Chiang, E. T., Lim, M., Lai, J., Rogers, R., Janmey, P. A., Shepro, D., and Doerschuk, C. M. (2001). Changes in the biomechanical properties of neutrophils and endothelial cells during adhesion. Blood 97:660–668.

    Article  PubMed  CAS  Google Scholar 

  • Wang, Q., and Doerschuk, C. M. (2000). Neutrophil-induced changes in the biomechanical properties of endothelial cells: Roles of ICAM-1 and reactive oxygen species. J. Immunol. 164:6487–6494.

    PubMed  CAS  Google Scholar 

  • Wang, Q., and Doerschuk, C. M. (2001). The p38 mitogen-activated protein kinase mediates cytoskeletal remodeling in pulmonary microvascular endothelial cells upon intracellular adhesion molecule-1 ligation. J. Immunol. 166:6877–6884.

    PubMed  CAS  Google Scholar 

  • Wang, Q., Pfeiffer, G. R., Stevens, T., and Doerschuk, C. M. (2002). Lung microvascular and arterial endothelial cells differ in their responses to intercellular adhesion molecule-1 ligation. Am. J. Respir. Crit Care Med. 166:872–877.

    Article  PubMed  Google Scholar 

  • Weed, S. A., and Parsons, J. T. (2001). Cortactin: Coupling membrane dynamics to cortical actin assembly. Oncogene 20:6418–6434.

    Article  PubMed  CAS  Google Scholar 

  • Weitz-Schmidt, G., Welzenbach, K., Brinkmann, V., Kamata, T., Kallen, J., Bruns, C., Cottens, S., Takada, Y., and Hommel, U. (2001). Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat. Med. 7:687–692.

    Article  PubMed  CAS  Google Scholar 

  • Whalen, M. J., Carlos, T. M., Dixon, C. E., Robichaud, P., Clark, R. S., Marion, D. W., and Kochanek, P. M. (2000). Reduced brain edema after traumatic brain injury in mice deficient in P-selectin and intercellular adhesion molecule-1. J. Leukoc. Biol. 67:160–168.

    PubMed  CAS  Google Scholar 

  • Willenborg, D. O., Simmons, R. D., Tamatani, T., and Miyasaka, M. (1993). ICAM-1-dependent pathway is not critically involved in the inflammatory process of autoimmune encephalomyelitis or in cytokine-induced inflammation of the central nervous system. J. Neuroimmunol. 45:147–154.

    Article  PubMed  CAS  Google Scholar 

  • Wojciak-Stothard, B., Williams, L., and Ridley, A. J. (1999). Monocyte adhesion and spreading on human endothelial cells is dependent on Rho-regulated receptor clustering. J. Cell Biol. 145:1293–1307.

    Article  PubMed  CAS  Google Scholar 

  • Wong, D., Prameya, R., and Dorovini-Zis, K. (1999). In vitro adhesion and migration of T lymphocytes across monolayers of human brain microvessel endothelial cells: Regulation by ICAM-1, VCAM-1, E-selectin and PECAM-1. J. Neuropathol. Exp. Neurol. 58:138–152.

    Article  PubMed  CAS  Google Scholar 

  • Yednock, T. A., Cannon, C., Fritz, L. C., Sanchez-Madrid, F., Steinman, L., and Karin, N. (1992). Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature 356:63–66.

    Article  PubMed  CAS  Google Scholar 

  • Youssef, S., Stuve, O., Patarroyo, J. C., Ruiz, P. J., Radosevich, J. L., Hur, E. M., Bravo, M., Mitchell, D. J., Sobel, R. A., Steinman, L., and Zamvil, S. S. (2002). The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature 420:78–84.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cell Therapy, Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK

    Patric Turowski, Peter Adamson & John Greenwood

Authors
  1. Patric Turowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter Adamson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John Greenwood
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patric Turowski.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Turowski, P., Adamson, P. & Greenwood, J. Pharmacological Targeting of ICAM-1 Signaling in Brain Endothelial Cells: Potential for Treating Neuroinflammation. Cell Mol Neurobiol 25, 153–170 (2005). https://doi.org/10.1007/s10571-004-1380-0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-004-1380-0

Key words

Search

Navigation