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VLA-4 and lymphocyte trafficking in immune-inflammatory states: novel therapeutic approaches in allograft arteriopathy

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Conclusions

Facing the complexity of factors governing graft arteriopathy in allograft transplantation, extensive studies presented thus far have only uncovered the tip of the iceberg. This problem has emerged as a major challenge for researchers, clinicians, surgeons and patients. As it becomes better defined and as we learn more about vascular cell-inflammatory cell interaction and production of soluble factors, the pathophysiology of this disease and possible novel therapeutic approaches will also come to the light. It is clear that there is a multiplicity of molecules involved in lymphocyte activation, that there is a dynamic interplay between adhesion and migration, with intracellular signals dictating specific cellular functions, and that cell-cell interaction is a multistep exchange [213]. The identification of integrins present on inflammatory cell surfaces which interact with extracellular matrix components has focused attention on the importance of such interactions [198]. Future therapeutic interventions that will address the matrix-lymphocyte interaction may well prevent the cascade of events leading to the graft arteriopathy. We propose that this would occur by halting the subsequent cytokine-dependent cascade of events resulting from activated T cell subendothelial trafficking and positioning. The latter involves up-regulation of adhesion molecules, release of soluble factors that further influences smooth muscle cell behavior and accumulation of newly formed extracellular matrix components, especially fibronectin.

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  1. Department of Pediatrics, Pathology and Medicine, University of Toronto, Toronto, Ontario, Canada

    Silvana Molossi

  2. Division of Cardiovascular Research, The Hospital For Sick Children, 555 University Avenue, M5G 1X8, Toronto, Ontario, Canada

    Marlene Rabinovitch

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Molossi, S., Rabinovitch, M. VLA-4 and lymphocyte trafficking in immune-inflammatory states: novel therapeutic approaches in allograft arteriopathy. Springer Semin Immunopathol 16, 443–465 (1995). https://doi.org/10.1007/BF00196100

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