Many recent studies have established the eosinophil as a primary effector cell in the pathology of allergic diseases. However, relatively little is known about the mechanisms by which eosinophils accumulate and are activated at local sites of tissue inflammation in allergic or other eosinophil-dependent pathologic states. Because the adherence of leukocytes to vascular endothelial cells (VEC) is a critial initial event in eosinophil infiltration, we have studied the interaction of purified human eosinophils with cultured human umbilical vein edothelial cells. Treatment of VEC with stimuli known to activate endothelial cells, including purified human IL-1, rTNF-α, bacterial endotoxin LPS, and the tumor-promoting phorbol diester 12-O-tetra-decanoylphorbol-13-acetate resulted in time- and dose-dependent increases (from two- to fourfold) in adhesiveness for eosinophils. Adherence induced by optimal concentrations of IL-1 (2 U/ml), TNF (1 μg/ml), and LPS (1 μg/ml) is dependent upon the CD18 leukocyte cell surface adherence glycoproteins, because a mAB (60.3) directed against the common β-subunit of the complex inhibits adherence induced by these stimuli. Several agents directly activated eosinophils to display increased adhesiveness to both VEC and gelatinized plates. The bacterial chemotactic peptide formyl-methionyl-leucyl-phenylalanine (10-8 to 10-6 M), TNF (1 to 1000 ng/ml), and 12-O-tetradecanoyl-phorbol-13-acetate (0.3 to 3 ng/ml) all increased eosinopphil binding to VEC by two to fivefold. Platelet-activating factor (PAF; 10-8 to 10-6 M), but not lyso-PAF, caused approximately a twofold increase in eosinophil binding to both VEC and gelatinized tissue culture plates, suggesting that activation of eosinophils may be responsible for the known ability of PAF to induce eosinophils responses. These results suggest that the initiation of an eosinophilic infiltrate in vivo can result from activation of endothelial cells, activation of eosinophils, or activation of both cell types.
|Original language||English (US)|
|Number of pages||6|
|Journal||Journal of Immunology|
|State||Published - 1988|
ASJC Scopus subject areas
- Immunology and Allergy