Interactions between eotaxin, histamine and mast cells in early microvascular events associated with eosinophil recruitment to the site of allergic skin reactions in humans
Abstract
Background: The mechanism whereby allergen induces eotaxin expression at the site of allergic inflammation is incompletely understood. Structural cells, including endothelial cells, are a major source of eotaxin.
Objective: We have investigated, in vivo and in vitro, the relationship between mast cell activation and the expression of eotaxin (eotaxin 1) by endothelial cells.
Methods: The effects of intradermal allergen challenge and histamine injection on eotaxin mRNA and protein generation were studied in atopic subjects using immunofluorescence, immunohistochemistry and in situ hybridization. Histamine-induced expression of eotaxin mRNA and protein by endothelial cells was also measured, as was histamine-induced eosinophil adhesion to cultured endothelial cells.
Results: A rapid increase in degranulating cutaneous mast cells, together with a concomitant increase in eosinophils, was observed 60 min after allergen challenge. This was accompanied by the appearance of immunoreactive eotaxin that peaked at 1 h around blood vessels and at 3 h within the tissue. Intradermal histamine injection produced an increase in the number of eotaxin+ cells in the tissues, which was maximal at the 3-h time-point. In vitro, endothelial cells produced eotaxin mRNA and protein product in a dose- and time-dependent fashion following incubation with histamine, an effect that was blocked by levocetirizine. Pre-incubation of endothelial cells with histamine also induced a significant increase in…
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