NEUROMODULATION OF MAST-CELLS IN HUMAN NA SAL-MUCOSA - HISTAMINE-RELEASE BY NEUROPEPTIDES IN-VITRO

There is growing evidence that neuropeptides like substance P (SP), va soactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) are involved in neurogenic inflammation of the nose, especially in allergic rhinitis. These neuropeptides induce effects on nasal epi thelial, endothelial, immunological, inflammatory and glandular cells. It is known that SP, CGRP and VIP stimulate isolated rat and human ma st cells to release histamine and lead to a wheal and flare reaction i n the human skin. These observations together with the fact that perip heral nerve fibres are found in close proximity to mast cells leads to the idea that some of the effects of neuropeptides are mediated by hi stamine release as consequence of a functional nerve/mast cell interac tion in human nasal mucosa. Thus we investigated the influence of SP, VIP, CGRP and calcium ionophore A23187 on histamine release of human n asal mucosa, using an in vitro short-term organ culture system. Compar ed to controls the histamine content in the culture supernatant of muc osal tissue samples stimulated with SP (10(-5), p < 0.01) and with cal cium ionophore A231S7 (10(-5) M, p < 0.001) was significantly higher. This effect of SP could not be inhibited by cromolyn sodium (2 x 10(-4 )M) or dexamethasone (10(-5)M). CGRP(10(-8) - 10(-6)M) and VIP (10(-8) - 10(-6)M) showed no influence on histamine release compared to contr ols. The results obtained in this study support the hypothesis of a ne uromodulation by neuropeptides on mast cells and suggest that the inte raction between sensory nerve fibres and mast cells are of pathogeneti c importance in inflammation of human nasal mucosa.