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Dexamethasone inhibition of leucocyte adhesion to rat mesenteric postcapillary venules: role of intercellular adhesion molecule 1 and KC

Abstract

BACKGROUND A previous study showed that the glucocorticoid dexamethasone, at doses of 100 μg/kg and above, inhibited leucocyte adhesion to rat mesenteric postcapillary venules activated with interleukin 1β (IL-1β), as assessed by videomicroscopy.

AIMS To identify whether the adhesion molecule, intercellular adhesion molecule 1 (ICAM-1), or the chemokine KC could be targeted by the steroid to mediate its antiadhesive effect.

METHODS Rat mesenteries were treated with IL-1β (20 ng intraperitoneally) and the extent of leucocyte adhesion measured at two and four hours using intravital microscopy. Rats were treated with dexamethasone, and passively immunised against ICAM-1 or KC. Endogenous expression of these two mediators was validated by immunohistochemistry, ELISA, and the injection of specific radiolabelled antibodies.

RESULTS Dexamethasone greatly reduced IL-1β induced leucocyte adhesion, endothelial expression of ICAM-1 in the postcapillary venule, and release of the mast cell derived chemokine KC. Injection of specific antibodies to the latter mediators was also extremely effective in downregulating (>80%) IL-1β induced leucocyte adhesion.

CONCLUSIONS Induction by IL-1β of endogenous ICAM-1 and KC contributes to leucocyte adhesion to inflamed mesenteric vessels. Without excluding other possible mediators, these data clearly show that dexamethasone interferes with ICAM-1 expression and KC release from mast cells, resulting in suppression of leucocyte accumulation in the bowel wall, which is a prominent feature of several gastrointestinal pathologies.

  • inflammation
  • glucocorticoids
  • intravital microscopy
  • mast cell
  • neutrophil
  • endothelium
  • Abbreviations used in this paper

    BSA
    bovine serum albumin
    DEX
    dexamethasone
    ICAM
    intercellular adhesion molecule
    IL
    interleukin
    PBS
    phosphate buffered saline
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  • Abbreviations used in this paper

    BSA
    bovine serum albumin
    DEX
    dexamethasone
    ICAM
    intercellular adhesion molecule
    IL
    interleukin
    PBS
    phosphate buffered saline
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