THE ROLE OF LEUKOTRIENES RELEASED DURING CUTANEOUS IMMEDIATE ALLERGIC REACTION ON ATOPIC DERMATITIS

1989 Fiscal Year Final Research Report Summary

• Project/Area Number: 63570470
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Dermatology
• Research Institution: HIROSHIMA UNIVERSITY
• Principal Investigator: NUMATA Tsunemi HIROSHIMA UNIVERSITY SCHOOL OF MEDICINE, UNIVERSITY HOSPITAL, LECTURER, 医学部附属病院, 講師 (70127687)
• Co-Investigator(Kenkyū-buntansha): HORIUCHI Kenji HIROSHIMA UNIVERSITY SCHOOL OF MEDICINE, UNIVERSITY HOSPITAL, ASSOCIATE, 医学部附属病院, 助手 (70190238) ; KORO Osamu HIROSHIMA UNIVERSITY SCHOOL OF MEDICINE, ASSOCIATE, 医学部, 助手 (10161887) ; YAMADA Satoru HIROSHIMA UNIVERSITY SCHOOL OF MEDICINE, UNIVERSITY HOSPITAL, ASSOCIATE, 医学部附属病院, 助手 (90158189)
• Project Period (FY): 1988 – 1989
• Keywords: Atopic dermatitis / Immediate allergic reaction / Leukotriene B_4 / Leukotriene C_4, D_4, E_4

Research Abstract

A clear explanation has not been made about the etiology of atopic dermatitis. Although histamine released from mast cells plays a critical role in cutaneous immediate allergic reaction, previous studies have shown release of neutrophil and eosinophil chemotactic factors suspected to be leukotriene (LT) B_4 from sensitized human and guinea pig skin during cutaneous immediate allergic reaction.
In the present studies, in order to investigate the role of LTs in atopic dermatitis, the release of LTB4 and peptide LTs (LTC_4,D_4 and E_4) during cutaneous immediate allergic reaction was investigated.
The abdominal skin of guinea pig sensitized with egg albumin was cleaned of subcutaneous tissue and cut into slices. The skin slices were incubated in Tyrode solution containing 100mug/ml egg albumin at 37ﾟC for 20 min. The levels of LTB_4, LTC_4, LTD_44 and LTE_4 in the supernatants were measured by combined HPLC and radio-immunoassay, respectively. The levels of LTB_4 and LTE_4 released by antigen were significantly increased but there were no significant increase in the levels of LTC_4 and LTD_4 compared with controls. As it is well known that LTC_4 and LTD_4 were easily metabolized into LTE_4, they might be released by antigen into the supernatants and metabolized into LTE_4 quickly.
As this result shows skin can synthesize significant quantities of LTB_4 during cutaneous immediate allergic reaction, the histological changes of the sensitized skin induced by LTB_4 were investigated. Intradermal injection of 100 mul 10^<-7>M LTB_4 induced a capillary dilatation and polymorphonuclear lymphocytes infiltrates followed by mononuclear lymphocytes infiltrates.
These results suggest that during cutaneous immediate allergic reaction, LTB_4 and peptide LTs might be released accompanying with histamine release and contribute to the cutneous changes such as inflammatory cell infiltrations in atopic dermatitis either directly or in concert with other mediators.