Interactions between eotaxin, histamine and mast cells in early microvascular events associated with eosinophil recruitment to the site of allergic skin reactions in humans.
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 eosinophil adherence, an effect that was inhibited with an anti-eotaxin blocking monoclonal antibody.


CONCLUSIONS
The antigen-induced expression of eotaxin by endothelial cells and the adherence and subsequent migration of eosinophils from the microvasculature to the tissues are rapid events partially under the control of histamine released from degranulating mast cells.
Menzies-Gow
A
A
Department of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College, London, UK.
Ying
S
S
Phipps
S
S
Kay
A B
AB
D000328:Adult; D002448:Cell Adhesion; D002460:Cell Line; D017332:Cetirizine / Q000494:pharmacology; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D003876:Dermatitis, Atopic / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology; D004804:Eosinophils / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006632:Histamine / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D007509:Irritants / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D018709:Statistics, Nonparametric
C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D006634:Histamine H1 Antagonists; D007509:Irritants; D010879:Piperazines; D012333:RNA, Messenger; C472067:levocetirizine; D006632:Histamine; D017332:Cetirizine