Kiyoshi Furutani

Chemical mediators in atopic dermatitis: Involvement of leukotriene B4 released by a type I allergic reaction in the pathogenesis of atopic dermatitis

BACKGROUND The mediators produced from a type I allergic reaction have not yet been able to explain the pathogenesis of atopic dermatitis (AD). OBJECTIVE The purpose of this study was to elucidate the involvement of leukotriene (LT) B4 produced from a type I allergic reaction in the pathogenesis of AD. METHOD The release of LTB4 was measured both in vitro, in passively sensitized and antigen-challenged human skin slices, as well as in vivo, in skin chambers on patients with AD. RESULTS LTB4 was released from in vitro human skin by stimulation of the antigen (54.9 +/- 14.6 pg/g wet weight of skin by antigen challenge and 28.0 +/- 11.1 pg/g in control skin, P <.002). Antigen-specific release of LTB4 and histamine was also observed in vivo in nonlesional skin from the patients with AD by using the skin chamber technique. CONCLUSION LTB4 release during type I allergic reaction in human skin has been determined in vitro. The released LTB4 possibly contributes to cellular response at the acute inflammatory lesion of AD.

Substance P- and antigen-induced release of leukotriene B4, prostaglandin D2 and histamine from guinea pig skin by different mechanisms in vitro

Abstract Substance P (SP) induces increased vascular permeability, vasodilatation and granulocyte infiltration upon intradermal injection. Studies with antagonists and mast cell-deficient mice have suggested that granulocyte infiltration in response SP is mediated by leukotriene (LT) B 4 derived from mast cells. However, the release of LTB 4 has not been detected using mast cells isolated from human skin. Here we report the release of LTB 4 , prostaglandin (PG) D 2 and histamine from guinea pig skin tissue in response to SP. The release of these agents occurred in a dose-dependent manner over a concentration range of SP from 1 × 10 –6 to 3 × 10 –4 M . No detectable PGE 2 was released at any concentration up to 3 × 10 –4 M SP. The kinetics of histamine release induced in response to SP was more rapid than that induced by antigen. By comparison, SP-induced and antigen-induced release of LTB 4 and PGD 2 were similar, but slower than the histamine release. In the absence of extracellular Ca 2+ , release of histamine and PGD 2 in response to SP was partially impaired, but to a lesser extent than that induced by antigen. On the other hand, LTB 4 release in response to both SP and antigen was abolished under the same conditions. These results indicate that SP induces the release of LTB 4 , as well as histamine and PGD 2 , in the skin most likely from mast cells by a mechanism which may be different from that of mediator release in response to antigen.