TUMOR NECROSIS FACTOR AND INTERFERON-GAMMA INDUCE DISTINCT PATTERNS OF ENDOTHELIAL ACTIVATION AND ASSOCIATED LEUKOCYTE ACCUMULATION IN SKIN OF PAPIO-ANUBIS

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  • 1 July 1989
    • journal article
    • research article
    • Vol. 135  (1) , 121-133
Abstract
Recombinant human interferon (IFN)-.gamma. (2 .times. 104 or 2 105 U), tumor necrosis factor (TNF, 104 or 105 U), or both were injected intracutaneously into baboons (Papio anubis), and biopsies were examined at various intervals for evidence of altered endothelial cell antigen expression, endothelial morphology, and leukocyte infiltration. IFN-.gamma. induced increased binding of anti-HLA-DP mAb by 24 hours and a mild-to-moderate accumulation of mononuclear cells. TNF induced increased binding of anti-endothelial leukocyte adhesion molecule (ELAM)-1 mAb by 2 hours that was associated with polymorphonuclear leukocyte accumulation, and increased binding of anti-intercellular adhesion molecule (ICAM)-1 mAb by 9 hours that was associated with the onset of progressive mononuclear leukocyte accumulation. TNF also caused endothelial cell hypertrophy and increased vascular permeability. The combination of IFN-.gamma. and TNF induced a set of changes that qualitatively resemble those of a delayed hypersensitivity reaction to simian agent 8 envelope antigen. These findings are consistent with the concept that cytokine-activated endothelium plays an important role in the adhesion and subsequent extravasation of leukocytes during immune inflammation.

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