Increased expression of endothelial cell adhesion molecules due to mediator release from human foreskin mast cells stimulated by autoantibodies in chronic urticaria sera.
Histamine-releasing antibodies that act against the epitope of the alpha chain of Fc(epsilon)RI (anti-Fc(epsilon)RI(alpha) antibody) that may affect pathogenesis in serum of patients with chronic urticaria. We assessed the capability of anti-Fc(epsilon)RI(alpha) 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-Fc(epsilon)RI(alpha) 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-alpha 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-alpha 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-Fc(epsilon)RI(alpha) antibody release mediators and tumor necrosis factor-alpha 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-alpha from mast cells.
Lee
Kwang Hoon
KH
Department of Dermatology, Cutaneous Biology Research Institute, Yonsei Medical Research Center, Yonsei University College of Medicine, Seoul, Korea. kwanglee@yumc.yonsei.ac.kr
Kim
Ji Young
JY
Kang
Dong-Seung
DS
Choi
Yoo Jean
YJ
Lee
Won-Jae
WJ
Ro
Jai Youl
JY
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001323:Autoantibodies / Q000097:blood; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002469:Cell Separation; D002478:Cells, Cultured; D002908:Chronic Disease; D017077:Culture Media, Conditioned / Q000494:pharmacology; D020405:Dermis / Q000166:cytology / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006636:Histamine Release / Q000276:immunology; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism; D017998:Leukotriene D4 / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D017455:Receptors, IgE / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D014581:Urticaria / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D018793:Interleukin-13; D017455:Receptors, IgE; D014409:Tumor Necrosis Factor-alpha; D017998:Leukotriene D4