Activation of human epidermal Langerhans cells by engagement of the high affinity receptor for IgE, Fc epsilon RI.
Human epidermal Langerhans cells (LCs) bind IgE via the high affinity receptor (Fc epsilon RI), and therefore are suspected to be involved in the genesis of atopic diseases. In this study, we report that surface expression of Fc epsilon RI is increased dramatically on LCs from patients with atopic dermatitis (AD) when compared with nonatopic individuals. Cross-linking of Fc epsilon RI on LCs from nonatopic individuals and patients with AD leads to a rapid tyrosine phosphorylation of several proteins, including p72, p77, and p95. However, upon receptor ligation, calcium mobilization is only detected in LCs freshly isolated from patients with AD (responder LCs), but not in those from normal skin of healthy individuals (nonresponder LCs). The beta-chain of Fc epsilon RI is not detected in normal LCs and only in a minority of LCs from atopic individuals, indicating that it is not related to the capacity of LCs to respond to Fc epsilon RI-mediated activation. In contrast, LCs from both nonatopic and atopic individuals internalize Fc epsilon RI by receptor-mediated endocytosis as a prerequisite for Ag focusing. Therefore, LCs from normal individuals and individuals with AD differ functionally by their Fc epsilon RI expression and by a distinct ability to respond to Fc epsilon RI-mediated activation.
Jürgens
M
M
Department of Dermatology, Ludwig-Maximilian University of Munich, Germany.
Wollenberg
A
A
Hanau
D
D
de la Salle
H
H
Bieber
T
T
D000911:Antibodies, Monoclonal; D002118:Calcium / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007801:Langerhans Cells / Q000276:immunology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000276:immunology; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; D017455:Receptors, IgE; D007073:Immunoglobulin E; D011505:Protein-Tyrosine Kinases; D002118:Calcium