Histamine-releasing antibodies that act against the epitope of the α chain of FcεRI (anti-FcεRIα antibody) that may affect pathogenesis in serum of patients with chronic urticaria. We assessed the capability of anti-FcεRIα antibody in sera from patients with chronic urticaria to release histamine and cytokines, and to induce the expression of endothelial cell adhesion molecules. We also assessed the release of inflammatory mediators from cultured foreskin mast cells, and expression of endothelial cell adhesion molecules on human dermal microvascular endothelial cells. Cells were pretreated with mast cell-conditioned media: Culture media of mast cells treated with sera from chronic urticaria patients containing anti-FcεRIα antibody. Histamine release from human foreskin mast cells challenged with sera, increased after both 20 min and 16 h intervals. Leukotriene D4 release also increased at both 20 min and 16 h. Tumor necrosis factor-α increased significantly in foreskin mast cell culture challenged with sera of chronic urticaria patients. After the stimulation of human dermal microvascular endothelial cells with the conditioned media, the expression of intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin increased significantly. Treatment of the conditioned media with anti-tumor necrosis factor-α monoclonal antibody partially inhibited the expression of intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin. The data suggest that sera from patients with chronic urticaria containing anti-FcεRIα antibody release mediators and tumor necrosis factor-α by activating human foreskin mast cells. This release can play a pathogenic role in chronic urticaria by activating endothelial cells, in part due to the actions of tumor necrosis factor-α from mast cells.
Bibliographical noteFunding Information:
This work was supported by the financial support of the Korea Research Foundation Grant (KRF-98-021-F00283) and by BK21 Project for Medical Science, Yonsei University.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology