Decreased cutaneous expression of stem cell factor and of the p75NGF receptor in urticaria.

Abstract

Mast cells, the main effector cells in urticaria, have been reported to be increased in number in lesional and nonlesional skin of urticaria patients, but the underlying mechanisms have so far not been studied. Serum NGF has however, been reported to be increased in urticaria. We have therefore explored the potential involvement of known mast cell growth modulating factors in urticaria. Tissue sections from patients with different types of urticaria and healthy controls were studied for the immunohistochemical expression of known mast cell growth factors (stem cell factor, SCF; nerve growth factor, NGF), of the inhibitory granulocyte-macrophage colony-stimulating factor (GM-CSF), and of the corresponding receptors, using the alkaline phosphatase-antialkaline phosphatase technique. Compared to skin of normal controls, staining for SCF, but not for NGF and GM-CSF, was significantly decreased in epidermis, endothelium and perivascular cells in lesional and nonlesional skin of all urticarias. On separate analysis of urticaria subtypes, decreased expression reached significance only in delayed pressure urticaria. Expression of the p75NGF receptor (p75NGFR) was also significantly decreased on endothelium and on perivascular cells of lesional and nonlesional skin in all urticarias. On evaluation of serial sections, p75NGFR expression was also decreased on c-Kit positive dermal mast cells. In contrast, expression of the NGF receptor tyrosine kinase and of the SCF and GM-CSF receptors was unchanged. These findings show that SCF and p75NGFR are selectively and systemically down-regulated in the skin of urticaria patients and may represent a negative feedback to increased mast cell reactivity and proliferation.