Mast cells induce upregulation of P-selectin and intercellular adhesion molecule 1 on carotid endothelial cells in a new in vitro model of mast cell to endothelial cell communication.
It is suggested that mast cells contribute to cell recruitment in inflammation through the upregulation of endothelial adhesion molecules. P-selectin and intercellular adhesion molecule(ICAM)-1 are two key adhesion molecules that have been associated indirectly with mast cell activity. The canine C2 mastocytoma cell line and primary cultures of canine carotid endothelial cells were used to establish a new in vitro model to help study the interaction between mast cells and endothelial cells. Carotid endothelial cells were incubated with mast cell mediators to uncover their effect on endothelial ICAM-1 and P-selectin expression. To assess the relative contributions of tumour necrosis factor (TNF)-alpha and histamine to such effect, an H1 antihistamine and a TNF-alpha blocking antibody were used. Prior to activation by mast cell mediators, P-selectin was expressed only within the cytoplasm, and ICAM-1 was constitutively expressed on the surface of the canine carotid endothelial cells. Both adhesion molecules were enhanced significantly and strongly upon mast cell activation at various time points. Unstored TNF-alpha was fully responsible for ICAM-1 upregulation. P-selectin was up-regulated by both preformed and newly synthesized mast cell mediators, but neither histamine nor TNF-alpha accounted for such an effect. Therefore,a new model is proposed in which the pro-inflammatory effect of mast cells on endothelial cells can be studied in vitro. In this model, it has been demonstrated that only TNF-alpha accounts for the overexpression of ICAM-1 induced by mast cells, and that mast cells up-regulate P-selectin expression through a histamine-independent mechanism.
Torres
R
R
Department of Pharmacology, Universitat Autònoma de Barcelona, Barcelona, Spain.
de Castellarnau
C
C
Ferrer
L L
LL
Puigdemont
A
A
Santamaría
L F
LF
de Mora
F
F
D000818:Animals; D002339:Carotid Arteries / Q000166:cytology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002450:Cell Communication; D015550:Cell Degranulation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008407:Mast Cells / Q000276:immunology*; D023421:Models, Animal; D019007:P-Selectin / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D015815:Cell Adhesion Molecules; D019007:P-Selectin; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D006632:Histamine