Mast cells are involved in many disorders where the triggering mechanism that 
leads to degranulation and/or cytokine secretion has not been defined. Several 
chronic inflammatory diseases are associated with increased mast cell numbers 
and upregulation of the TNF receptor family member CD30, but the role of 
elevated CD30 expression is poorly understood. Here we report what we believe to 
be a novel way to activate mast cells with CD30 that leads to 
degranulation-independent secretion of chemokines. CD30 induced a de novo 
synthesis and secretion of the chemokines IL-8, macrophage inflammatory 
protein-1alpha (MIP-1alpha), and MIP-1beta, a process involving the MAPK/ERK 
pathway. Mast cells were found to be the predominant CD30 ligand-positive 
(CD30L-positive) cell in the chronic inflammatory skin diseases psoriasis and 
atopic dermatitis, and both CD30 and CD30L expression were upregulated in 
lesional skin in these conditions. Furthermore, the number of IL-8-positive mast 
cells was elevated both in psoriatic and atopic dermatitis lesional skin as well 
as in ex vivo CD30-treated healthy skin organ cultures. In summary, 
characterization of CD30 activation of mast cells has uncovered an 
IgE-independent pathway that is of importance in understanding the entirety of 
the role of mast cells in diseases associated with mast cells and CD30 
expression. These diseases include Hodgkin lymphoma, atopic dermatitis, and 
psoriasis.