The central role of chemokines (chemotactic cytokines) in the immunopathogenesis of ulcerative colitis and Crohn's disease

Authors

  • Dr. Richard P. MacDermott,

    Corresponding author
    1. Section of Gastroenterology, Lahey Hitchcock Clinic Medical Center, Burlington, U.S.A.
    2. Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, U.S.A.
    • Section of Gastroenterology, IBD Center, Lahey Hitchcock Clinic, 41 Mall Road, Burlington, MA 01805, U.S.A
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  • Ian R. Sanderson,

    1. Division of Pediatric Gastroenterology and Nutrition, Massachusetts, U.S.A.
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  • Hans-Christian Reinecker

    1. Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, U.S.A.
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Abstract

The final composition of leukocytes present in a site of inflammation in response to chemokine stimulation and activation may depend on both the nature of the secreted chemokines as well as the relative expression of the multitude of specific chemokine cell surface receptors on many different cell types. Because related receptors with different affinities and cross-reactive binding capabilities are present on each type of leukocyte, relative differences in receptor distribution and receptor affinity for specific chemokines may significantly influence which cells are ultimately attracted to and activated by each individual chemokine. Production of IL-8, MCP-1, and ENA-78 by endothelial cells, LPMNC, and epithelial cells in IBD could establish a chemotactic gradient capable of influencing the increased migration of monocytes/macrophages. granulocytes, and lymphocytes from the blood stream through the endothelium into both the mucosa and submucosa during chronic IBD. The ability of chemokines to induce chemotaxis, leukocyte activation, granule exocytosis, increased production of metalloenzymes, and up-regulation of respiratory burst activity indicates that there may be a variety of different mechanisms by which chemokines could markedly increase chronic inflammation and chronic intestinal tissue destruction in IBD.

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