No abstract

Background: Atopic dermatitis (AD) can be exacerbated or induced in genetically predisposed individuals by psychological stress, which causes the release of substance P (SP). Therefore, SP may play an etiological role in the mechanisms underlying AD. Methods: Changes in the number of mast cells and SP-containing mast cells in lesional skin, and the serum concentrations of SP and IgE during the development of AD-like disease up to 8 weeks after the start of picryl chloride (PiCl) induction in NC/Nga mice were examined. Results: Clinical signs and symptoms seen in PiCl-treated NC/Nga mice as a model of AD-like disease began with erythema and haemorrhage, followed by oedema, superficial erosion, deep excoriation, scaling and dryness of the skin, as well as retarded growth, and the changes were exacerbated with an increase in the number of PiCl applications. An increase in the number of mast cells and eosinophil infiltration was observed in the lesional skin. The increase in SP-positive mast cells in the dermis in this model was significant from 1 week after the start of induction treatment, compared with intact mice, and SP-positive nerve fibres were observed in the dermis. Conclusion: SP is a crucial mediator of both dermatitis and scratching behaviour in this model.

Infiltrating polymorphonuclear leukocytes (PMN) in the peritoneal cavity were found to express L-histidine decarboxylase (HDC), the rate-limiting enzyme of histamine synthesis, in a csein-induced peritonitis model. Expression of HDC was detected in the elicited PMN, but not in the peripheral blood leukocytes. The peritoneal lavage fluids in this model were found to augment histamine synthesis in PMN isolated from the bone marrow. Rapid posttranslational processing of HDC was observed in PMN, and the dominant form of HDC was the mature 53-kDa form, which was found to co-localize with a granule enzyme, matrix metalloproteinase-9 (MMP-9). Treatment of PMN with the phorbol ester PMA, which stimulates the release of MMP-9, did not liberate the granular HDC. Immunofluorescence studies using an anti-HDC antibody strongly suggested that HDC is bound to the cytosolic side of the granule membranes. These observations suggest that HDC is induced upon infiltration of PMN into the mouse peritoneal cavity and that histamine is synthesized by HDC attached to the granule membranes of PMN.